Different chromatin-scanning modes lead to targeting of compacted chromatin by pioneer factors FOXA1 and SOX2.


Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
25 07 2023
Historique:
received: 22 12 2022
revised: 20 04 2023
accepted: 19 06 2023
medline: 31 7 2023
pubmed: 5 7 2023
entrez: 5 7 2023
Statut: ppublish

Résumé

Pioneer transcription factors interact with nucleosomes to scan silent, compact chromatin, enabling cooperative events that modulate gene activity. While at a subset of sites pioneer factors access chromatin by assisted loading with other transcription factors, the nucleosome-binding properties of pioneer factors enable them to initiate zygotic genome activation, embryonic development, and cellular reprogramming. To better understand nucleosome targeting in vivo, we assess whether pioneer factors FoxA1 and Sox2 target stable or unstable nucleosomes and find that they target DNase-resistant, stable nucleosomes, whereas HNF4A, a non-nucleosome binding factor, targets open, DNase-sensitive chromatin. Despite FOXA1 and SOX2 targeting similar proportions of DNase-resistant chromatin, using single-molecule tracking, we find that FOXA1 uses lower nucleoplasmic diffusion and longer residence times while SOX2 uses higher nucleoplasmic diffusion and shorter residence times to scan compact chromatin, while HNF4 scans compact chromatin much less efficiently. Thus, pioneer factors target compact chromatin through distinct processes.

Identifiants

pubmed: 37405916
pii: S2211-1247(23)00759-3
doi: 10.1016/j.celrep.2023.112748
pmc: PMC10529229
mid: NIHMS1920493
pii:
doi:

Substances chimiques

Chromatin 0
Deoxyribonucleases EC 3.1.-
Nucleosomes 0
Transcription Factors 0
Hepatocyte Nuclear Factor 3-alpha 0
SOXB1 Transcription Factors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

112748

Subventions

Organisme : NIGMS NIH HHS
ID : R01 GM036477
Pays : United States
Organisme : NIGMS NIH HHS
ID : S06 GM008216
Pays : United States

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Jonathan Lerner (J)

Institute for Regenerative Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058, USA.

Andrew Katznelson (A)

Institute for Regenerative Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058, USA.

Jingchao Zhang (J)

Institute for Regenerative Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058, USA.

Kenneth S Zaret (KS)

Institute for Regenerative Medicine and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6058, USA. Electronic address: zaret@pennmedicine.upenn.edu.

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Classifications MeSH