Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation

Single-chromosome transcriptional profiling reveals chromosomal

gene expression regulation

Marshall J Levesque, Arjun RajSystems Biology LabUPenn Bioengineering

Nature Methods (2013) doi:10.1038/nmeth.2372

Thursday, April 11, 13

Our genome is organized into pairs of chromosomes

By 718 Bot at en.wikipedia [Public domain], from Wikimedia Commons. http://en.wikipedia.org/wiki/Karyotype


http://commons.wikimedia.org/wiki/File%3ASky_spectral_karyotype.png

http://commons.wikimedia.org/wiki/File%3ASky_spectral_karyotype.png

Chromosome rearrangements are a hallmark of cancer

Macville et al. Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping. Cancer Res (1999) vol. 59 (1) pp. 141-50


Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)

DIAPH3MTZ1 RPL18A UBA52 ZNF91 UBA2 EIF3K SUPT5H FBL EGLN2 RPS19 TOMM40 MARK4 SLC1A5 PPP2R1A RPS9 ZNF444

HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm

Chromosome 19 gene name


Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B

CentromereTranslocation

t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)

PTBP1 EEF2 DNMT1 ILF3 DHPS 0

0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2

0 Mb Chromosome 19 59.13 Mb

DNM

T1IL

F3DH

PS

N=30N=50

N=30

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

Does chromosome structure affect gene expression?

RNA FISH (fluorescence in situ hybridization) from Raj Lab website image gallery


Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30




Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

RNA counting cannot tell us where the RNA comes from



iceFISH assay detects active genes on single chromosomes

Spliced mRNA

Export andTranslation

ExonExon

Exon

IntronIntron

Introns degraded beforeleaving site of transcription

mRNA

Raj et al. Imaging individual mRNA molecules using multiple singly labeled probes. Nat Methods (2008)


iceFISH assay detects active genes on single chromosomes

Spliced mRNA

Export andTranslation

ExonExon

Exon

IntronIntron

Introns degraded beforeleaving site of transcription

intron


04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)

C DAPI ED ATTO488 Cy3

F G HAlexa 594 ATTO647N ATTO700

Chromosome 19IntronA

5 base colors

2 colors 3 colors20 pseudocolors

B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

Pseudocoloring provides 20+ unique tags to trace a chromosome

04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus


04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

Pseudocoloring provides 20+ unique tags to trace a chromosome


iceFISH assigns gene activity to normal or derivative copies of chr19

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30


Translocations can lead to whole chromosome increases in expression

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)RP

L18A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30


Translocations do not necessarily lead to changes in transcriptional activity

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

to Chr 6 centromere

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30

iceF

ISH

spo

ts p

er c

hrom

osom

e


Are chromosomes built to regulate their genes?

Chr. 19EEF2 mRNAEEF2 intron


Single chromosome transcription profiles unravel gene interactions

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PSRPL18AUBA52ZNF91UBA2EIF3KSUPT5HFBLEGLN2RPS19

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4

R = 0.33TOMM40MARK4SLC1A5PPP2R1ARPS9ZNF444

PTBP1EEF2DNMT1ILF3DHPS

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS

RPL18AUBA52ZNF91UBA2EIF3KSUPT5HFBLEGLN2RPS19TOMM40MARK4SLC1A5PPP2R1ARPS9ZNF444


RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



Intra-chromosomal (cis) interactions Inter-chromosomal (trans) interactions

4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001

High likelihoodof interaction

Low likelihoodof interaction

Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS

RPL18AUBA52ZNF91UBA2EIF3KSUPT5HFBLEGLN2RPS19

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

Anti-Correlated Expression

Correlated Expression

Uncorrelated Expression


Measured gene activity shows interactions at chromosome scale

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)


RPS19PTBP1EEF2DNMT1ILF3DHPS

RPL18AUBA52ZNF91UBA2EIF3KSUPT5HFBLEG

LN2RPS19

OFF

OFF

ZNF444

ON

ON

RPS19OFF

OFF

ZNF444

ON

ON

RPS19OFF

OFF

ZNF444

ON

ON

RPS19OFF

OFF

ZNF444

ON

ON

Nucleus

Chr. 19G

ene A

Gene B

p = 2.7x10 -5

R = -0.42p = 1.0R = 0.008

p = 4.0x10 -5

R = -0.40p = 6.9x10 -4

R = 0.33TO

MM

40M

ARK4SLC1A5PPP2R1ARPS9ZNF444

PTBP1EEF2DNM

T1ILF3DHPS




LN2RPS19TO

MM

40M


PTBP1EEF2DNM

T1ILF3DHPS




LN2RPS19TO

MM

40M


PTBP1EEF2DNM

T1ILF3DHPS




LN2RPS19TO

MM

40M


PTBP1EEF2DNM

T1ILF3DHPS

Intra-chromosom

al (cis) interactionsInter-chrom

osomal (trans) interactions

4531527

2749239

4524625

35341615

Nucleus

Chr. 19G

ene A

Gene B

1 2 p=0.05

4 p = 0.015 6 p = 0.001

8 p = 0.0001

High likelihood

of interaction

Low likelihood

of interaction

Human foreskin fibroblastsHeLa cells

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells



-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)


RPS19PTBP1EEF2DNMT1ILF3DHPS


LN2RPS19

OFF

OFF

ZNF444

ON

ON

RPS19OFF

OFF

ZNF444

ON

ON

RPS19OFF

OFF

ZNF444

ON

ON

RPS19OFF

OFF

ZNF444

ON

ON

Nucleus

Chr. 19G

ene A

Gene B

p = 2.7x10 -5

R = -0.42p = 1.0R = 0.008

p = 4.0x10 -5

R = -0.40p = 6.9x10 -4

R = 0.33TO

MM

40M


PTBP1EEF2DNM

T1ILF3DHPS




LN2RPS19TO

MM

40M


PTBP1EEF2DNM

T1ILF3DHPS




LN2RPS19TO

MM

40M


PTBP1EEF2DNM

T1ILF3DHPS




LN2RPS19TO

MM

40M


PTBP1EEF2DNM

T1ILF3DHPS

Intra-chromosom

al (cis) interactionsInter-chrom

osomal (trans) interactions

4531527

2749239

4524625

35341615

Nucleus

Chr. 19G

ene A

Gene B

1 2 p=0.05

4 p = 0.015 6 p = 0.001

8 p = 0.0001

High likelihood

of interaction

Low likelihood

of interaction

Human foreskin fibroblastsHeLa cells -log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells



Anti-Correlated

04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

14Mb


Long range cis interaction is maintained in HeLa cell line

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

normal chromosome 19


Long range cis interaction is lost in rearranged chromosome 19

-log(p)

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

t(13;19)Gene A

Gene B

p = 1.0R = 0.03

p = 0.14R = 0.29

Intra-chromosomal (cis) interactions

HeLa cells, t(13;19)

Biol

ogica

l rep

licat

e 1

Com

bine

d da

tase

tBi

olog

ical r

eplic

ate

2

23

196

74

63

1

2

p = 0.05

4

p = 0.01

5

6

p = 0.001RP

L18A

UBA5

2ZN

F91

UBA2

EIF3

KSU

PT5H

FBL

EGLN

2RP

S19

TOM

M40

MAR

K4SL

C1A5

PPP2

R1A

RPS9

ZNF4

44


RPS1

9

OFF

OFFZNF444

ON

ON

p = 0.33R = 0.33

97

259

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444


RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444


Supplementary Figure ***

Supplementary Fig. ***. Characterization of intra-chromosomal interactions between chromosome 19 gene pairs on the der(19)t(13;19) fusion chromosome in HeLa cells. The analysis is exactly the same as that performed in Fig. 3 and as described in the methods. We found no significant correlation between RPS19 and ZNF444, suggesting that the translocation disrupts the whatever the regulatory mechanism is that is respon-sible for the anti-correlation we obseved between this pair of genes on the normal copies of chromosome 19 in both human foreskin fibroblasts and HeLa cells.



HeLa t(13;19)-log(p)

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

RPS1

9PT

BP1

EEF2

DNM

T1IL

F3DH

PS


OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

Chr. 19Gene A

Gene B

p = 2.7x10-5

R = -0.42p = 1.0R = 0.008

p = 4.0x10-5

R = -0.40p = 6.9x10-4



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS



RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444

PTBP

1EE

F2DN

MT1

ILF3

DHPS




4531

527

2749

239

4524

625

3534

1615

Nucleus

Chr. 19Gene A

Gene B

1

2

p=0.05

4

p = 0.015

6

p = 0.001

8

p = 0.0001



Hum

an fo

resk

in fi

brob

last

sHe

La c

ells

-log(p)

RPS1

9

OFF

OFFZNF444

ON

ON

RPS1

9

OFF

OFFZNF444

ON

ON

Nucleus

t(13;19)Gene A

Gene B

p = 1.0R = 0.03

p = 0.14R = 0.29

Intra-chromosomal (cis) interactions

HeLa cells, t(13;19)

Biol

ogica

l rep

licat

e 1

Com

bine

d da

tase

tBi

olog

ical r

eplic

ate

2

23

196

74

63

1

2

p = 0.05

4

p = 0.01

5

6

p = 0.001

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444


RPS1

9

OFF

OFFZNF444

ON

ON

p = 0.33R = 0.33

97

259

RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444


RPL1

8AUB

A52

ZNF9

1UB

A2EI

F3K

SUPT

5HFB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5PP

P2R1

ARP

S9ZN

F444


Supplementary Figure ***

Supplementary Fig. ***. Characterization of intra-chromosomal interactions between chromosome 19 gene pairs on the der(19)t(13;19) fusion chromosome in HeLa cells. The analysis is exactly the same as that performed in Fig. 3 and as described in the methods. We found no significant correlation between RPS19 and ZNF444, suggesting that the translocation disrupts the whatever the regulatory mechanism is that is respon-sible for the anti-correlation we obseved between this pair of genes on the normal copies of chromosome 19 in both human foreskin fibroblasts and HeLa cells.




Anti-Correlated

04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

14Mb



Anti-Correlated

14Mb0

48

1216

20

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus



Anti-Correlated

04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

14Mb

04

812

1620

1612

84

0

024

x (µm)

y (µm)

z (µ

m)




5 base colors


B

I

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

JChr 19

Chr 19

Nucleus

iceFISH revealed new chromosome-level gene expression behaviors

Chr 19

Chr 19t(13;19)

Fusionchromosomes

t(6;19)


HeLa Karyotype

Chr 19

Chr 19q-arm

*** **

** ***

******

******

***

***

Chr 6p-arm

Chr 6q-arm

Chr 19p-arm



Chr. 13gene name

0

0.4

0.2

0.8

1

0.6

iceFI

SH s

pots

per

chr

omos

ome

t(13;19)

t(6;19)Chr 13q-arm

A

C

B


t(13;19) t(13;19)

Chr 19Chr 13t(13;19)t(6;19)


0.4

0.2

0.8

1

0.6

t(6;19)

RPL1

8A

UBA5

2

ZNF9

1

UBA2

EIF3

KSU

PT5H FB

LEG

LN2

RPS1

9TO

MM

40M

ARK4

SLC1

A5

PPP2

R1A

RPS9

ZNF4

44

PTBP

1

EEF2


DNM

T1IL

F3DH

PS

N=30N=50

N=30


Acknowledgements

Members of the Raj Lab

Morrissette Cytogenetics Lab

Biosearch Technologies


Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation

Health & Medicine

Transcript of Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation