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| Status |
Public on Jul 28, 2013 |
| Title |
Examination of histone H2B ubiquitination in wild type and USP49 knockdown cells [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Posttranslational histone modifications play important roles in regulating chromatin structure and function. Histone H2B ubiquitination and deubiquitination have been implicated in transcriptional regulation, but the function of H2B deubiquitination is not well defined, particularly in higher eukaryotes. Here we report the purification of USP49 as a histone H2B specific deubiquitinase and demonstrate that H2B deubiquitination by USP49 is required for efficient co-transcriptional splicing of a large set of exons. USP49 forms a complex with RVB1 and SUG1, and specifically deubiquitinates histone H2B in vitro and in vivo. USP49 knockdown results in small changes in gene expression, but affects the abundance of over 9,000 isoforms. Exons down-regulated in USP49 knockdown cells show both elevated levels of alternative splicing and a general decrease in splicing efficiency. Importantly, USP49 is relatively enriched at this set of exons. USP49 knockdown increased uH2B levels at these exons as well as upstream 3’ and downstream 5’ intronic splicing elements. Change in H2B ubiquitination level, as modulated by USP49, regulates U1A and U2B association with chromatin and binding to nascent pre-mRNA. Although H3 levels are relatively stable after USP49 depletion, H2B levels at these exons are dramatically increased, suggesting that uH2B may enhance nucleosome stability. Therefore, this study identifies USP49 as a histone H2B specific deubiquitinase and uncovers a critical role for H2B deubiquitination in co-transcriptional pre-mRNA processing events.
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| Overall design |
Examination of histone H2B ubiquitination in wild type and USP49 knockdown cells [ChIP-Seq]
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| Contributor(s) |
Wang H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
May 21, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Hengbin Wang |
| Organization name |
Virginia Commonwealth University
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| Department |
Massey Cancer Institute
|
| Street address |
401 College Street
|
| City |
Richmond |
| State/province |
VA |
| ZIP/Postal code |
23298 |
| Country |
USA |
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| Platforms (2) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
| GPL15433 |
Illumina HiSeq 1000 (Homo sapiens) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE38101 |
USP49 deubiquitinates histone H2B and regulates pre-mRNA splicing |
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| Relations |
| BioProject |
PRJNA167215 |
| SRA |
SRP013287 |
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