Widespread association of Polycomb complex–deposited histone H2A monoubiquitylation with enhancers and neuronal gene regulation Article Swipe
Kailynn MacGillivray
,
Daniel Fusca
,
Luomeng Tan
,
Reta Aram
,
Arneet L. Saltzman
,
Kailynn MacGillivray
,
Daniel Fusca
,
Luomeng Tan
,
Reta Aram
,
Arneet L. Saltzman
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adt6316
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adt6316
Disruption of histone H2A monoubiquitylation (H2AK119ub) causes neurodevelopmental disorders through poorly understood mechanisms. Polycomb complex–deposited H2AK119ub and trimethylation of histone H3 at lysine 27 (H3K27me3) can cooperatively maintain gene repression. However, the extent to which H2AK119ub functions independently of H3K27me3 to repress or potentiate gene expression, and the evolutionary conservation of these roles, remains unclear. Here, we address the interplay among Polycomb-deposited marks and chromatin states in Caenorhabditis elegans embryos. We find that H2AK119ub distribution is distinct from and largely dispensable for H3K27me3 patterns. Unexpectedly, H2AK119ub is enriched at predicted enhancers with developmentally dynamic changes in accessibility, including in neurons. More than two-thirds of well-documented axon guidance genes and neuronal identity transcription factors are associated with H2AK119ub. Many of the genes differentially expressed in H2AK119ub-deficient animals are involved in neuronal differentiation and signaling and feature H2AK119ub-enriched promoters and enhancers, including a subset that is H3K27me3 repressed. We uncover a likely conserved yet underappreciated dual role for H2AK119ub at enhancers and H3K27me3-repressed chromatin, with implications for nervous system development.
Related Topics
Concepts
Enhancer
Biology
Chromatin
Histone
Genetics
Regulation of gene expression
Gene
Polycomb-group proteins
Epigenetics
Histone H3
Transcription factor
Epigenomics
Promoter
Transcriptional regulation
RNA polymerase II
Enhancer RNAs
Transcription (linguistics)
Cell biology
Acetylation
ChIA-PET
Chromatin immunoprecipitation
H3K4me3
PRC2
Chromatin remodeling
Regulatory sequence
Histone methylation
Histone code
Epigenesis
Axon
Phenotype
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1126/sciadv.adt6316
- OA Status
- gold
- References
- 128
- OpenAlex ID
- https://openalex.org/W7106703615
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W7106703615Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1126/sciadv.adt6316Digital Object Identifier
- Title
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Widespread association of Polycomb complex–deposited histone H2A monoubiquitylation with enhancers and neuronal gene regulationWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-11-26Full publication date if available
- Authors
-
Kailynn MacGillivray, Daniel Fusca, Luomeng Tan, Reta Aram, Arneet L. Saltzman, Kailynn MacGillivray, Daniel Fusca, Luomeng Tan, Reta Aram, Arneet L. SaltzmanList of authors in order
- Landing page
-
https://doi.org/10.1126/sciadv.adt6316Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1126/sciadv.adt6316Direct OA link when available
- Concepts
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Enhancer, Biology, Chromatin, Histone, Genetics, Regulation of gene expression, Gene, Polycomb-group proteins, Epigenetics, Histone H3, Transcription factor, Epigenomics, Promoter, Transcriptional regulation, RNA polymerase II, Enhancer RNAs, Transcription (linguistics), Cell biology, Acetylation, ChIA-PET, Chromatin immunoprecipitation, H3K4me3, PRC2, Chromatin remodeling, Regulatory sequence, Histone methylation, Histone code, Epigenesis, Axon, PhenotypeTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- References (count)
-
128Number of works referenced by this work
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