Most of the tight positional conservation of transcription factor binding sites near the transcription start site reflects their co-localization within regulatory modules

Abstract

Background: Transcription factors (TFs) form complexes that bind regulatory modules (RMs) within DNA, to control specific sets of genes. Some transcription factor binding sites (TFBSs) near the transcription start site (TSS) display tight positional preferences relative to the TSS. Furthermore, near the TSS, RMs can co-localize TFBSs with each other and the TSS. The proportion of TFBS positional preferences due to TFBS co-localization within RMs is unknown, however. ChIP experiments confirm co-localization of some TFBSs genome-wide, including near the TSS, but they typically examine only a few TFs at a time, using non-physiological conditions that can vary from lab to lab. In contrast, sequence analysis can examine many TFs uniformly and methodically, broadly surveying the colocalization of TFBSs with tight positional preferences relative to the TSS.

MEPP: more transparent motif enrichment by profiling positional correlations

“…For example, some transcription factors play a role in directing the selection of TSS, or preventing ectopic TSS utilization ( 6 ). The position of TF binding motifs relative to other motifs can also be important for establishing functional regulatory modules and TF co-binding, as reflected in regulatory motif grammars ( 7–9 ).…”