The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop
R-loops are regulators of many cellular processes and are threats to genome integrity. Therefore, understanding the mechanisms underlying the regulation of R-loops is important. Inspired by the findings on RNase H1-mediated R-loop degradation or accumulation, we focused our interest on the regulatio...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-08-01
|
| Series: | Cell Insight |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892723000366 |
| _version_ | 1797737312584466432 |
|---|---|
| author | Le Li Yequn Wu Kui Dai Qing Wang Shiqi Ye Qipeng Shi Zhenfei Chen Yi-Chun Huang Weiwei Zhao Lijia Li |
| author_facet | Le Li Yequn Wu Kui Dai Qing Wang Shiqi Ye Qipeng Shi Zhenfei Chen Yi-Chun Huang Weiwei Zhao Lijia Li |
| author_sort | Le Li |
| collection | DOAJ |
| description | R-loops are regulators of many cellular processes and are threats to genome integrity. Therefore, understanding the mechanisms underlying the regulation of R-loops is important. Inspired by the findings on RNase H1-mediated R-loop degradation or accumulation, we focused our interest on the regulation of RNase H1 expression. In the present study, we report that G9a positively regulates RNase H1 expression to boost R-loop degradation. CHCHD2 acts as a repressive transcription factor that inhibits the expression of RNase H1 to promote R-loop accumulation. Sirt1 interacts with CHCHD2 and deacetylates it, which functions as a corepressor that suppresses the expression of downstream target gene RNase H1. We also found that G9a methylated the promoter of RNase H1, inhibiting the binding of CHCHD2 and Sirt1. In contrast, when G9a was knocked down, recruitment of CHCHD2 and Sirt1 to the RNase H1 promoter increased, which co-inhibited RNase H1 transcription. Furthermore, knockdown of Sirt1 led to binding of G9a to the RNase H1 promoter. In summary, we demonstrated that G9a regulates RNase H1 expression to maintain the steady-state balance of R-loops by suppressing the recruitment of CHCHD2/Sirt1 corepressors to the target gene promoter. |
| first_indexed | 2024-03-12T13:26:51Z |
| format | Article |
| id | doaj.art-c91d300c1c8a47f394c1758ff0538825 |
| institution | Directory Open Access Journal |
| issn | 2772-8927 |
| language | English |
| last_indexed | 2024-03-12T13:26:51Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Insight |
| spelling | doaj.art-c91d300c1c8a47f394c1758ff05388252023-08-25T04:24:56ZengElsevierCell Insight2772-89272023-08-0124100112The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loopLe Li0Yequn Wu1Kui Dai2Qing Wang3Shiqi Ye4Qipeng Shi5Zhenfei Chen6Yi-Chun Huang7Weiwei Zhao8Lijia Li9College of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCollege of Life Sciences, Wuhan University, Wuhan, 430072, ChinaCorresponding author.; College of Life Sciences, Wuhan University, Wuhan, 430072, ChinaR-loops are regulators of many cellular processes and are threats to genome integrity. Therefore, understanding the mechanisms underlying the regulation of R-loops is important. Inspired by the findings on RNase H1-mediated R-loop degradation or accumulation, we focused our interest on the regulation of RNase H1 expression. In the present study, we report that G9a positively regulates RNase H1 expression to boost R-loop degradation. CHCHD2 acts as a repressive transcription factor that inhibits the expression of RNase H1 to promote R-loop accumulation. Sirt1 interacts with CHCHD2 and deacetylates it, which functions as a corepressor that suppresses the expression of downstream target gene RNase H1. We also found that G9a methylated the promoter of RNase H1, inhibiting the binding of CHCHD2 and Sirt1. In contrast, when G9a was knocked down, recruitment of CHCHD2 and Sirt1 to the RNase H1 promoter increased, which co-inhibited RNase H1 transcription. Furthermore, knockdown of Sirt1 led to binding of G9a to the RNase H1 promoter. In summary, we demonstrated that G9a regulates RNase H1 expression to maintain the steady-state balance of R-loops by suppressing the recruitment of CHCHD2/Sirt1 corepressors to the target gene promoter.http://www.sciencedirect.com/science/article/pii/S2772892723000366R-loopRNase H1CHCHD2G9aSirt1 |
| spellingShingle | Le Li Yequn Wu Kui Dai Qing Wang Shiqi Ye Qipeng Shi Zhenfei Chen Yi-Chun Huang Weiwei Zhao Lijia Li The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop Cell Insight R-loop RNase H1 CHCHD2 G9a Sirt1 |
| title | The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop |
| title_full | The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop |
| title_fullStr | The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop |
| title_full_unstemmed | The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop |
| title_short | The CHCHD2/Sirt1 corepressors involve in G9a-mediated regulation of RNase H1 expression to control R-loop |
| title_sort | chchd2 sirt1 corepressors involve in g9a mediated regulation of rnase h1 expression to control r loop |
| topic | R-loop RNase H1 CHCHD2 G9a Sirt1 |
| url | http://www.sciencedirect.com/science/article/pii/S2772892723000366 |
| work_keys_str_mv | AT leli thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT yequnwu thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT kuidai thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT qingwang thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT shiqiye thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT qipengshi thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT zhenfeichen thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT yichunhuang thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT weiweizhao thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT lijiali thechchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT leli chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT yequnwu chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT kuidai chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT qingwang chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT shiqiye chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT qipengshi chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT zhenfeichen chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT yichunhuang chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT weiweizhao chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop AT lijiali chchd2sirt1corepressorsinvolveing9amediatedregulationofrnaseh1expressiontocontrolrloop |