Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition
Abstract Background The histone H3K36me3 mark regulates transcription elongation, pre-mRNA splicing, DNA methylation, and DNA damage repair. However, knowledge of the regulation of the enzyme SETD2, which deposits this functionally important mark, is very limited. Results Here, we show that the poor...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2020-10-01
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| Series: | Epigenetics & Chromatin |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13072-020-00362-8 |
| _version_ | 1818305251188408320 |
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| author | Saikat Bhattacharya Jerry L. Workman |
| author_facet | Saikat Bhattacharya Jerry L. Workman |
| author_sort | Saikat Bhattacharya |
| collection | DOAJ |
| description | Abstract Background The histone H3K36me3 mark regulates transcription elongation, pre-mRNA splicing, DNA methylation, and DNA damage repair. However, knowledge of the regulation of the enzyme SETD2, which deposits this functionally important mark, is very limited. Results Here, we show that the poorly characterized N-terminal region of SETD2 plays a determining role in regulating the stability of SETD2. This stretch of 1–1403 amino acids contributes to the robust degradation of SETD2 by the proteasome. Besides, the SETD2 protein is aggregate prone and forms insoluble bodies in nuclei especially upon proteasome inhibition. Removal of the N-terminal segment results in the stabilization of SETD2 and leads to a marked increase in global H3K36me3 which, uncharacteristically, happens in a Pol II-independent manner. Conclusion The functionally uncharacterized N-terminal segment of SETD2 regulates its half-life to maintain the requisite cellular amount of the protein. The absence of SETD2 proteolysis results in a Pol II-independent H3K36me3 deposition and protein aggregation. |
| first_indexed | 2024-12-13T06:23:37Z |
| format | Article |
| id | doaj.art-c01f7f1ad87e4b7d9b9d7969e970a79c |
| institution | Directory Open Access Journal |
| issn | 1756-8935 |
| language | English |
| last_indexed | 2024-12-13T06:23:37Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Epigenetics & Chromatin |
| spelling | doaj.art-c01f7f1ad87e4b7d9b9d7969e970a79c2022-12-21T23:56:47ZengBMCEpigenetics & Chromatin1756-89352020-10-0113111410.1186/s13072-020-00362-8Regulation of SETD2 stability is important for the fidelity of H3K36me3 depositionSaikat Bhattacharya0Jerry L. Workman1Stowers Institute for Medical ResearchStowers Institute for Medical ResearchAbstract Background The histone H3K36me3 mark regulates transcription elongation, pre-mRNA splicing, DNA methylation, and DNA damage repair. However, knowledge of the regulation of the enzyme SETD2, which deposits this functionally important mark, is very limited. Results Here, we show that the poorly characterized N-terminal region of SETD2 plays a determining role in regulating the stability of SETD2. This stretch of 1–1403 amino acids contributes to the robust degradation of SETD2 by the proteasome. Besides, the SETD2 protein is aggregate prone and forms insoluble bodies in nuclei especially upon proteasome inhibition. Removal of the N-terminal segment results in the stabilization of SETD2 and leads to a marked increase in global H3K36me3 which, uncharacteristically, happens in a Pol II-independent manner. Conclusion The functionally uncharacterized N-terminal segment of SETD2 regulates its half-life to maintain the requisite cellular amount of the protein. The absence of SETD2 proteolysis results in a Pol II-independent H3K36me3 deposition and protein aggregation.http://link.springer.com/article/10.1186/s13072-020-00362-8ChromatinProteasomeHistoneMethylationAggregation |
| spellingShingle | Saikat Bhattacharya Jerry L. Workman Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition Epigenetics & Chromatin Chromatin Proteasome Histone Methylation Aggregation |
| title | Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition |
| title_full | Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition |
| title_fullStr | Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition |
| title_full_unstemmed | Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition |
| title_short | Regulation of SETD2 stability is important for the fidelity of H3K36me3 deposition |
| title_sort | regulation of setd2 stability is important for the fidelity of h3k36me3 deposition |
| topic | Chromatin Proteasome Histone Methylation Aggregation |
| url | http://link.springer.com/article/10.1186/s13072-020-00362-8 |
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