Gene Expression Regulation via Pluripotency Related Transcription Factors and Micro RNA in Mouse

Embryonic Stem Cell during Differentiation

Y-h. Tahguchi, Dept. Phys., Chuo Univ.,Paul Bertone, EBI, EMBL.

genomegene

TF2TF1mRNA

miRNA1 miRNA2

ES

lineages

time

Gene

exp. u

pdown

TF1 TF2 miRNA1

miRNA2

gene1 ° £ ° °

gene2 £ ° ° £

gene3 ° £ £ £

gene4 £ £ £ £

at ES cell (known)

Comp. Pred.

binding

Target

Gene expression

Embedding (2D)

Each dot = gene expression

Principal component analysis ES

Biological replicates 1 and 2

1st PC

Up Down regulation

TF1 TF2 TF3 TF4 miRNA1

miRNA2

miRNA3

miRNA4

miRNA5

gene1 1 1 0 0 0 1 1 1 0

gene2 1 0 0 0 1 1 1 0 0

gene3 1 1 0 0 0 1 0 0 1

gene4 1 0 0 0 1 0 1 0 0

gene5 0 0 0 0 0 0 0 0 0

gene6 0 1 1 0 1 0 0 0 1

gene7 1 1 0 0 0 0 0 0 1

gene8 0 0 0 1 0 1 0 1 0

gene9 1 0 0 0 0 0 0 0 0

Hypergeometric analysis

Mean of gene 2 and 4

Results

For TF binding; Many TF binding combinations result in significant P-value (P<0.05). More TF bindings causes downregulation. Regulation by TF binding is weakly lineage specific. TF binding is stochastic decreasing process during differentiation.

PC1 by other kind of PCA.Numbers : time orderColor : lineages

Regulation by TF binding is weakly lineage specific.

Less T

F bin

din

gs

For TF bindings + miRNA target No miRNA target results in significant P-value (Exception, data from Anton group). But mean FDR << 1, thus many true positives are hidden. Regulation by miRNA target is strongly lineage specific. More miRNAs target causes upregulation (mostly. Sometimes, downregulation, too).

More miRNAs target causes upregulation

Time

Color, number :Number of miRNAs which target each gene.Top 10 miRNAs used.

Caution;

This is “mean” gene expression and is deviation from “over all mean”.“Over all mean” is strongly downregulated due to TF bindings.

Gene e

xpre

ssion

Anton group's data

Conclusion