Abstract
Background We have recently predicted comprehensive maps of cis-regulatory modules (CRMs) and constituent transcription factor (TF) binding sites (TFBSs) in the human and mouse genomes, enabling us to investigate the organization and architecture of the CRMs in both genomes.Results We reveal common rules of the organization and architecture of CRMs in the genomes. 1) The numbers and lengths of CRMs and genes on chromosomes are correlated with the sizes of chromosomes. 2) CRMs are unevenly but correlatedly distributed with genes along chromosomes. 3) The number of CRMs and genes within topologically associating domains (TADs) shows a stronger correlation than those in non-TAD regions. 4) CRMs are slightly biasedly distributed downstream of their nearest transcription start sites. 5) A considerable portion (~ 7%) of CRMs overlap core promoters, thus, CRMs can be classified into core promoter-containing (CPC) and core promoter-lacking (CPL) categories. 6) Most (> 90%) of core promoters overlap long CRMs, hence, they rarely exist alone. 7) CPC CRMs tend to be longer than CPL CRMs. 8) TFBSs exhibit extensive overlaps, forming longer TFBS islands. 9) TFBS islands comprise less than half of CRMs in length. 10) Spacers between TFBS islands are subject to similar evolutionary constraints as TFBS islands. Inter-TFBS spacers are less likely to overlap DNase I hypersensitive sites and TF footprints than TFBS islands, suggesting that they may play roles in transcriptional regulation other than direct TF binding.Conclusions The rules governing the organization and architecture of CRMs in the human and mouse genomes are highly conserved.