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

Autor:	Grand RS; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany., Pregnolato M; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4003 Basel, Switzerland., Baumgartner L; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland., Hoerner L; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland., Burger L; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Swiss Institute of Bioinformatics, 4058 Basel, Switzerland., Schübeler D; Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4003 Basel, Switzerland. Electronic address: dirk@fmi.ch.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2024 Sep 19; Vol. 84 (18), pp. 3455-3468.e6. Date of Electronic Publication: 2024 Aug 28.
DOI:	10.1016/j.molcel.2024.08.009
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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