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
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In vitro transcription elongation assays showed that, by blocking HDAC2 activity, histones surrounding specific exons remained hyperacetylated, which resulted in an increased RNAPII transcription rate and decreased exon inclusion at these genomic loci.”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Zhou et al. 2011
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Experiments with HuB and HuC deletion mutants indicated that the linker region and RRM3 are necessary for nELAV regulation of alternative splicing (Zhu et al. 2008; Zhou et al. 2011).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Zhou et al. 2011
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In addition to binding intronic sequences, co-IP assays revealed that Hu proteins interact with RNA polymerase II and histone deacetylase 2 (HDAC2) to regulate alternative splicing (Zhou et al. 2011).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Zhou et al. 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Alternative isoform regulation in human tissue transcriptomes
Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., & Burge, C. B. (2008) · Nature · doi:10.1038/nature07509 · Cited by 5,181
Pan, Q., Shai, O., Lee, L. J., Frey, B. J., & Blencowe, B. J. (2008) · Nature Genetics · doi:10.1038/ng.259 · Cited by 3,951
The Role of Chromatin during Transcription
Li, B., Carey, M., & Workman, J. L. (2007) · Cell · doi:10.1016/j.cell.2007.01.015 · Cited by 3,503
Mechanisms of Alternative Pre-Messenger RNA Splicing
Black, D. L. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161720 · Cited by 2,704
Expansion of the eukaryotic proteome by alternative splicing
Nilsen, T. W., & Graveley, B. R. (2010) · Nature · doi:10.1038/nature08909 · Cited by 2,270
Functions of Site-Specific Histone Acetylation and Deacetylation
Shahbazian, M. D., & Grunstein, M. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.052705.162114 · Cited by 1,635
Substrate and Functional Diversity of Lysine Acetylation Revealed by a Proteomics Survey
Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.06.026 · Cited by 1,487
Genome-wide mapping of HATs and HDACs reveals distinct functions in active and inactive genes
Wang, Z., Zang, C., Cui, K., Schones, D. E., Barski, A., Peng, W., & Zhao, K. (2009) · Cell · doi:10.1016/j.cell.2009.06.049 · Cited by 1,344
Carrozza, M. J., Li, B., Florens, L. A., Suganuma, T., Swanson, S. K., Lee, K. K., Shia, W.-J., Anderson, S., Yates, J. R., Washburn, M. P., et al. (2005) · Cell · doi:10.1016/j.cell.2005.10.023 · Cited by 1,338
Understanding alternative splicing: towards a cellular code
Matlin, A. J., Clark, F., & Smith, C. W. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1645 · Cited by 1,299
Research works printed but not linked: 4
- 10.1016/j.molcel.2009.10.008 · DOI
- 10.1128/MCB.01509-07 · DOI
- 10.1038/nsmb.1995 · DOI · Paper page
- 10.1038/nsmb.1620 · DOI · Paper page
Cited by
Sorted by citations
Coupling mRNA processing with transcription in time and space
Bentley, D. L. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3662 · Cited by 828
Maunakea, A. K., Chepelev, I., Cui, K., & Zhao, K. (2013) · Cell Research · doi:10.1038/cr.2013.110 · Cited by 552
Delcuve, G. P., Khan, D. H., & Davie, J. R. (2012) · Clinical Epigenetics · doi:10.1186/1868-7083-4-5 · Cited by 505
How introns enhance gene expression
Shaul, O. (2017) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2017.06.016 · Cited by 516
Regulation of Alternative Splicing Through Coupling with Transcription and Chromatin Structure
Naftelberg, S., Schor, I. E., Ast, G., & Kornblihtt, A. R. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034242 · Cited by 462
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
- Publisher
- National Academy of Sciences
- Published
- 2011-08
- Volume
- 108
- Issue
- 36
- Pages
- E627-35
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3169152
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
