S.1: Supplementary Material – Transcription factor interregulation and indirect regulation of genes
S.1.1: The transcription factor regulatory network in E. coli and Yeast
Fig S.1.1:
(A) The transcription factor (TF) regulatory network in E. coli. This is the fraction of the known
gene regulatory network in E. coli where the regulated gene is also a TF. This network
consists of 129 interactions and 85 TFS, or 69 interactions and 63 TFs when one does not
consider the 60 autoregulatory interactions.
(B) The graph shows the distribution of the number of TFs regulated by each TF in E. coli,
with and without autoregulatory interactions. Note that the TF CRP regulates 15 other TFs,
while many TFs regulate only one other TF. In other words, it is evident from (A) and (B) that
the E. coli TFs are not uniformly connected, but a few TFs regulate many other genes, while
most TFs regulate only a few other genes.
(C) The TF regulatory network in yeast. This network consists of 70 interactions and 51 TFs,
or 60 interactions and 48 TFs when one does not consider the 10 autoregulatory interactions.
(D)The graph shows the distribution of the number of TFs regulated by each yeast TF with
and without autoregulatory interactions. Note that the distribution is more uniform than in the
E. coli network: there are many TFs that regulate more than two other TFs, as indicated by
Guelzim et al. (2002), but there are no major regulatory hubs like CRP in E. coli. Perhaps this
is because there are more layers of signal transduction cascades above the level of gene
regulation. The greater interregulation of yeast transcription factors is linked to the large
number of feed-forward loops as compared to E. coli.
S.1.2: Direct and Indirect Number of Genes, Operons and Transcription
Factors Regulated by E. coli and Yeast Transcription Factors
Fig S.1.2:
(A) Direct and indirect number of operons regulated by each E. coli TF.
(B) Direct and indirect number of TFs regulated by each E. coli TF.
(C) Direct and indirect number of genes regulated by yeast TFs. For the 109 yeast TFs,
about half the transcription factors directly regulate one to five genes, and the largest
number of direct target genes is 31. As shown in (A), the more than half the 121 E.
coli TFs directly regulate one to five genes, and there are a small number of global
regulators that directly regulate up to about 150 genes, some of which act in direct
response to signals such as small molecule concentrations. On the other hand, the
number of indirectly regulated genes tends to be greater for the yeast TFs than E. coli
TFs, because the yeast TF regulatory network is more uniformly interconnected (see,
Fig S2C), and hence each TF is able to influence many more genes than it regulates
directly.
(D) Direct and indirect number of TFs regulated by yeast TFs. This graph clearly that
yeast TFs also indirectly regulate more TFs than E. coli TFs.
Direct regulation: Where a TF regulates a target gene through its binding site.
e.g: TF1
regulated gene
Indirect regulation: Where a TF regulates a target gene indirectly by regulating another TF,
which regulates the target gene.
e.g: TF1
TF2
regulated gene