Meta-analysis of Chromatin Programming by Steroid Receptors

Abstract

Summary: Transcription factors (TFs) must access chromatin to bind to their response elements and regulate gene expression. A widely accepted model proposes that only a special subset of TFs, pioneer factors, can associate with condensed chromatin and initiate chromatin opening. We previously reported that steroid receptors (SRs), not considered pioneer factors, can assist the binding of an archetypal pioneer, the forkhead box protein 1 (FOXA1), at a subset of receptor-activated enhancers. These findings have been challenged recently, with the suggestion that newly acquired data fully support the prevailing pioneer model. Here, we reexamine our results and confirm the original conclusions. We also analyze and discuss a number of available datasets relevant to chromatin penetration by SRs and find a general consensus supporting our original observations. Hence, we propose that chromatin opening at some sites can be initiated by SRs, with a parallel recruitment of factors often treated as having a unique pioneer function. This Matters Arising paper is in response to Glont et al. (2019), published in Cell Reports. : It is widely accepted that only pioneer transcription factors such as FOXA1 can reprogram chromatin for secondary transcription factor binding. Paakinaho et al. report through meta-analysis of published independent ChIP-seq datasets from several laboratories that the chromatin binding of FOXA1 can be reprogrammed by steroid hormone treatment. Keywords: pioneer factors, transcription factors, steroid receptors, FOXA1, chromatin, chromatin remodelers, dynamic assisted loading