Cited by 136RNA Research and SplicingGenomics and Chromatin DynamicsRNA regulation and disease

The DOI matches its Crossref record; 67 of the 67 references it cites were found in a registry or an index.

Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner

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Abstract

Recent studies have provided strong evidence for a regulatory link among chromatin structure, histone modification, and splicing regulation. However, it is largely unknown how local histone modification patterns surrounding alternative exons are connected to differential alternative splicing outcomes. Here we show that splicing regulator Hu proteins can induce local histone hyperacetylation by association with their target sequences on the pre-mRNA surrounding alternative exons of two different genes. In both primary and mouse embryonic stem cell-derived neurons, histone hyperacetylation leads to an increased local transcriptional elongation rate and decreased inclusion of these exons. Furthermore, we demonstrate that Hu proteins interact with histone deacetylase 2 and inhibit its deacetylation activity. We propose that splicing regulators may actively modulate chromatin structure when recruited to their target RNA sequences cotranscriptionally. This “reaching back” interaction with chromatin provides a means to ensure accurate and efficient regulation of alternative splicing.

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  1. 10.1016/j.molcel.2009.10.008 · DOI
  2. 10.1128/MCB.01509-07 · DOI
  3. 10.1038/nsmb.1995 · DOI · Paper page
  4. 10.1038/nsmb.1620 · DOI · Paper page

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Metadata

Authors
Zhou, H.-L., Hinman, M. N., Barron, V. A., Geng, C., Zhou, G., Luo, G., Siegel, R. E., & Lou, H.
Affiliations
  • Case Western Reserve University (US)
  • Case Comprehensive Cancer Center (US)
  • Department of Pharmacology,
Venue
Proceedings of the National Academy of Sciences
Published
2011-08
Volume
108
Issue
36
Pages
E627-35
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2107278624
Cited by
136
References
67
Citations by year
2026: 3 · 2025: 4 · 2024: 5 · 2023: 8 · 2022: 5 · 2021: 11 · 2020: 6 · 2019: 5 · 2018: 8 · 2017: 10 · 2016: 5 · 2015: 13 · 2014: 19 · 2013: 20 · 2012: 12
FWCI
6.89
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense
  • American Heart Association
  • University of Otago
  • Universidad de Buenos Aires
  • National Institutes of Health
  • National Cancer Institute (CA112094, R01CA112094)
  • National Institute of General Medical Sciences (T32GM008613)
  • National Institute of Neurological Disorders and Stroke (R56NS049103, R01NS049103, 5R03NS59648, NS-049103, R03NS059648, F31NS064724)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD00710432, T32HD007104)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Keywords
HU protein, alternative splicing, histone hyperacetylation, HDAC2, chromatin regulation, splicing regulation, pre-mRNA, alternative exons, transcription elongation, embryonic stem cell-derived neurons
MeSH terms
Acetylation, Animals, Cells, Cultured, Chromatin, Exons, Histones, Neurons, RNA Precursors, Transcription, Genetic, Alternative Splicing, Mice, ELAV Proteins, Histone Deacetylase 2

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