Topic reciprocal regulation of purine and pyrimidine metabolism
Figure 4: Varying combinations of GREs act conditionally...
Transcript of Figure 4: Varying combinations of GREs act conditionally...
A
B
C
Arginine and proline
PRPP
Glutamine
Carbamoyl-P
GMP
CytosineUMP
Alanine, aspartate, and glutamate Histidine Urea
Cycle
Pentose Phophate Pathway
Purine biosynthesis
Pyrimidine biosynthesis
Thiamine
�
� �
�
�
�
�
�
�
�
��
−1
0
1
−1
0
1
−1
0
1
��
�
*
* *
*
* *
*
expr
essi
on c
orre
latio
n
Env
ironm
ents
in w
hich
gen
es w
ithin
cor
ems
are
co-r
egul
ated
ec512157 ec516031 ec516034
* q-value ≤ 0.05
96
86
55
107
71
GRE 2
GRE 4PurRArgR
MetJ
IclRMetJ
GRE 12
GRE 19
GRE 30GRE 87
GRE 206
GREs
nucleotide biosynthesisAla/Asp/Glu metabolism
3.1x10-29
6.0x10-8
q-valueamino acid biosynthesis
purine biosynthesis
pyrimidine biosynthesis 2.1x10-10
2.6x10-31
9.8x10-93
pHdiauxic shift
diauxic shiftcarbon source
carbon sourceamino acids
q-value
9.6x10-7
1.2x10-6
1.7x10-3
4.8x10-4
1.9x10-3
5.2x10-11
ec516034
ec512157
ec516031
93
27
26
12
14
genes in corem
shared genes
D* KS-test, FDR ≤ 5%
(1) GLUCOSE (2) GLYCEROL (3) ACETATE (4) SPIRAMYCIN-1(5) CCCP-2.0
−40
−20
0 ●● ●● ● ●●
PurR 1 5
●
●●
●
●
●
●
●●
●
●
*****
ec516031
1 5
●
●● ●
●● ● ● ● ●
* **
ec512157
1 5
●●
●
● ●
●** **
ec516034
1 5
Rel
ativ
e Fi
tnes
s
RegPrecise PurR regulon
20 22 3
Conditions (listed to right)
Figure 4: Varying combinations of GREs act conditionally to subdivide and coordinate branches of the nucleotide biosynthesis pathway in an environment-dependent manner
GREs implicated in co-regulating
genes within corem
Genes in ec516031Genes in ec512157
Genes in ec516034
Co-regulated segm
ent(s) of the nucleotide biosynthesis pathway
Functions enriched in corem
Conditions enriched in corem
Figure 4. Varying combinations of GREs act conditionally to subdivide and coordinate branches of the nucleotide biosynthesis pathway in an environment-dependent manner(A) Genes of nucleotide biosynthesis are distributed in overlapping combinations across three corems: purine (ec516034 –“purine corem”), pyrimidine (ec512157–“pyrimidine corem”), or both pathways (ec516031 –“nucleotide corem”). (Left) Gene membership and overlap for the three corems as in Figure 3C. Pie charts indicate average GRE composition across all gene promoters in each corem (see Figure S3B for detail). (Top-Right Inset) GRE key for pie charts. Matches to TFs in RegulonDB noted above the GRE name. (Bottom-Right) Tables list enriched gene functions (40) and environmental conditions for each of the corems (see Supplementary Methods). (B) A portion of the nucleotide biosynthetic pathways, near the branch point dividing purine (top) and pyrimidine (bottom) biosynthesis. Pie charts represent GRE composition in each gene promoter (Key in (A)). Operons denoted by dashed lines, with only the leader gene’s promoter architecture shown.(C) Condition-speci�c co-expression of genes across the three corems. (Right) The active segments of nucleotide biosynthesis (as in B) are color-matched to corems. (Center) Violin plots show distributions of expression correlations between genes within each corem in relevant environmental conditions, when they are predicted to be co-regulated. Color �ll and asterisks indicate corems with signi�cantly low relative standard deviation (RSD; |σ/μ|; FDR ≤ 0.05). (Left) Colored circles indicate when genes within which corem(s) are predicted to be co-regulated (color) under how many conditions (number). (D) Distributions of relative �tness values for gene deletions in the three corems, as well as 20 of the 42 PurR regulon genes not modeled by ec516031 (black) across 5 representative conditions (condition identi�ers listed to right, additional conditions in Figure S6B). Asterisks denote conditions in which the distribu-tion of �tness values is statistically signi�cant (relative to the distribution of �tness values for all genes in that condition).See also Figure S6A-B.