Genome access is transcription factor-specific and defined by nucleosome position

2024/08/28 by Ralph S. Grand, Marco Pregnolato, Lisa Baumgartner +3 · 1 voice · 5 citations
Biochemistry, Genetics and Molecular Biology · #CRISPR and Genetic Engineering #Genomics and Chromatin Dynamics #Pluripotent Stem Cells Research

paper · doi:10.1016/j.molcel.2024.08.009

openalex publication_date 2024/08/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22

Abstract

Mammalian gene expression is controlled by transcription factors (TFs) that engage sequence motifs in a chromatinized genome, where nucleosomes can restrict DNA access. Yet, how nucleosomes affect individual TFs remains unclear. Here, we measure the ability of over one hundred TF motifs to recruit TFs in a defined chromosomal locus in mouse embryonic stem cells. This identifies a set sufficient to enable the binding of TFs with diverse tissue specificities, functions, and DNA-binding domains. These chromatin-competent factors are further classified when challenged to engage motifs within a highly phased nucleosome. The pluripotency factors OCT4-SOX2 preferentially engage non-nucleosomal and entry-exit motifs, but not nucleosome-internal sites, a preference that also guides binding genome wide. By contrast, factors such as BANP, REST, or CTCF engage throughout, causing nucleosomal displacement. This supports that TFs vary widely in their sensitivity to nucleosomes and that genome access is TF specific and influenced by nucleosome position in the cell.

Citations

• Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming
• Transcription factor–DNA binding: beyond binding site motifs
• Variable léxica y dialectología hispánica
• Pioneer Transcription Factors Initiating Gene Network Changes

Cited by

• Pervasive and programmed nucleosome distortion on single chromatin fibres
• Interplay between circadian and other transcription factors—Implications for cycling transcriptome reprogramming
• A conserved upstream element in the mouse Csf1r locus contributes to transcription in hematopoietic and trophoblast cells
• A novel deep learning-based framework reveals a continuum of chromatin sensitivities across transcription factors
• Modular control of CpG islands by chromatin-opening transcription factors specifies transcription start sites

Discussions

• Maybe of interest, in mESCs doi.org/10.1016/j.mo... [bsky, 1 points, 0 comments]

Related

• Variable léxica y dialectología hispánica
• Pervasive and programmed nucleosome distortion on single chromatin fibres
• Nucleosome positioning and gene regulation
• Extrinsic and intrinsic nucleosome positioning signals
• Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus