Distribution of DBDs in the TF Regulatory Network

1. + _ + + _ _ _ metR iclR dnaA _ rhaS marA marR _ uidR _ metJ fadR + iciA rhaR _ _ uxuR soxS rob + _ exuR _ lrp soxR mlc + fecI + _ + + + + + + malT malI melR yiaJ araC glpR glnG gutM fucR fur srlR nagC _ _ + + + _ mtlR CRP _ caiF adiY ompR tdcA _ _ csdG fruR + rcsB + galS fis _ narL _ _ arcA himA hns + lysR lctR pdhR + betI galR tdcR cspA fnr appY Putative DNA-binding domain Homeodomain-like Met repressor-like FIS-like “winged helix” DNA binding domain IHF like DNA-binding domain Nucleic acid-binding proteins Lambda repressor-like DNA binding domain C-terminal effector domain of the Bipartite response regulator Negative regulation with binding site data Positive regulation with binding site data Gene Product Distribution of DBDs in the TF Regulatory Network _ Negative regulation without binding site data Positive regulation without binding site data +

2. Transcription Factors and their regulated TFs A relatively complex topology exists in a simple organism The TF network has four major regulatory hubs which are also global regulators in their respective functional class. Number of Examples Number of different TF genes (X) regulated by a transcription factor Very few TFs regulate more than one TF Transcription Factors and their regulated genes Information on the regulated gene is available for 113 TFs from RegulonDB. We classified the 113 TFs in to nine functional classes according to what they respond to and what they regulate. Each of these functional classes have one to three proteins (global regulators) that regulate over 50 genes and the other proteins (fine tuners) control fewer than 20 genes

3. Network Growth by Gene Duplication Duplication growth models Gene regulatory network in E. coli Model-1: Duplication of regulated gene Model-2: Duplication of transcription factor Model-1 400 out of the 1233 (~1/3) interactions have homologous TFs sharing RG or homologous RGs sharing TFs. This suggests that duplication is a major mechanism for network growth Model-2 710 out of the 1233 interactions have either TF with a homologue or RG with a homologue but not share RG or TF, suggesting innovation of new edges or duplication followed by loss of regulatory interactions. 32 TFs (out of 110) share regulated genes with a homologue 123 out of the 1233 interactions have no homologues for TFs and RG suggesting that these interactions were innovations. 197 RG (out of 340) share transcription factors with a homologue