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Cited by 110Genomics and Chromatin DynamicsDiffusion and Search DynamicsNuclear Structure and Function

Two-Parameter Mobility Assessments Discriminate Diverse Regulatory Factor Behaviors in Chromatin

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Lerner, Jonathan, Gomez-Garcia, Pablo Aurelio, McCarthy, Ryan L., Liu, Zhe, Lakadamyali, Melike, Zaret, Kenneth S.·2020·Molecular Cell
DOI 10.1016/j.molcel.2020.05.036PMC PMC7483934
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Abstract

Enzymatic probes of chromatin structure reveal accessible versus inaccessible chromatin states, while super-resolution microscopy reveals a continuum of chromatin compaction states. Characterizing histone H2B movements by single-molecule tracking (SMT), we resolved chromatin domains ranging from low to high mobility and displaying different subnuclear localizations patterns. Heterochromatin constituents correlated with the lowest mobility chromatin, whereas transcription factors varied widely with regard to their respective mobility with low- or high-mobility chromatin. Pioneer transcription factors, which bind nucleosomes, can access the low-mobility chromatin domains, whereas weak or non-nucleosome binding factors are excluded from the domains and enriched in higher mobility domains. Nonspecific DNA and nucleosome binding accounted for most of the low mobility of strong nucleosome interactor FOXA1. Our analysis shows how the parameters of the mobility of chromatin-bound factors, but not their diffusion behaviors or SMT-residence times within chromatin, distinguish functional characteristics of different chromatin-interacting proteins.

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  • HNF4A is unable to bind nucleosomes.

    “While HNF4A can efficiently affect H3K4me1 and H3K27ac levels, it has been shown that HNF4A is unable to bind nucleosomes71, a defining feature of pioneer factors.”

    From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [71]

    The Results section, “Nucleosome affinity of transcription factors predicts their chromatin mobility” (page unavailable), says HNF4A has “virtually no affinity for nucleosomes.” That supports very weak binding, but not the categorical claim that HNF4A is unable to bind them. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Lerner, J., Gomez-Garcia, P. A., McCarthy, R. L., Liu, Z., Lakadamyali, M., & Zaret, K. S.
Affiliations
  • University of Pennsylvania (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Zaret, Kenneth S.
ORCID
Venue
Molecular Cell
Publisher
Elsevier BV
Published
2020-08
Volume
79
Issue
4
Pages
677-688.e6
ISSN
1097-2765 (ISSN-L)
DOI
10.1016/j.molcel.2020.05.036
PMC
PMC7483934
OpenAlex
W3036122966
Cited by
110
References
6
Citations by year
2026: 15 · 2025: 15 · 2024: 16 · 2023: 22 · 2022: 13 · 2021: 23 · 2020: 6
FWCI
5.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Diffusion and Search Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
Keywords
chromatin mobility, histone H2B, single-molecule tracking, chromatin condensation, heterochromatin, transcription factors, pioneer transcription factors, nucleosome binding, FOXA1, chromatin accessibility, subnuclear localization, chromatin domains, chromatin structure
MeSH terms
Animals, Cell Line, Cell Nucleus, Chromatin, Heterochromatin, Histones, Humans, Molecular Biology, Nucleosomes, Fluorescence Recovery After Photobleaching, Mice

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