MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation
Abstract Male‐specific lethal 1 (MSL1) is critical for the formation of MSL histone acetyltransferase complex which acetylates histone H4 Lys16 (H4K16ac) to activate gene expression. However, the role of MSL1 in liver regeneration is poorly understood. Here, this work identifies MSL1 as a key regula...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202301094 |
| _version_ | 1797742674437996544 |
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| author | Yucheng He Shichao Wang Shenghui Liu Dan Qin Zhangmei Liu Liqiang Wang Xiangmei Chen Lisheng Zhang |
| author_facet | Yucheng He Shichao Wang Shenghui Liu Dan Qin Zhangmei Liu Liqiang Wang Xiangmei Chen Lisheng Zhang |
| author_sort | Yucheng He |
| collection | DOAJ |
| description | Abstract Male‐specific lethal 1 (MSL1) is critical for the formation of MSL histone acetyltransferase complex which acetylates histone H4 Lys16 (H4K16ac) to activate gene expression. However, the role of MSL1 in liver regeneration is poorly understood. Here, this work identifies MSL1 as a key regulator of STAT3 and histone H4 (H4) in hepatocytes. MSL1 forms condensates with STAT3 or H4 through liquid–liquid phase separation to enrich acetyl‐coenzyme A (Ac‐CoA), and Ac‐CoA in turn enhances MSL1 condensate formation, synergetically promoting the acetylation of STAT3 K685 and H4K16, thus stimulating liver regeneration after partial hepatectomy (PH). Additionally, increasing Ac‐CoA level can enhance STAT3 and H4 acetylation, thus promoting liver regeneration in aged mice. The results demonstrate that MSL1 condensate‐mediated STAT3 and H4 acetylation play an important role in liver regeneration. Thus, promoting the phase separation of MSL1 and increasing Ac‐CoA level may be a novel therapeutic strategy for acute liver diseases and transplantation. |
| first_indexed | 2024-03-12T14:43:56Z |
| format | Article |
| id | doaj.art-68cb86758aaf4054b2e355b0604a023d |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-12T14:43:56Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-68cb86758aaf4054b2e355b0604a023d2023-08-16T02:23:01ZengWileyAdvanced Science2198-38442023-08-011023n/an/a10.1002/advs.202301094MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their AcetylationYucheng He0Shichao Wang1Shenghui Liu2Dan Qin3Zhangmei Liu4Liqiang Wang5Xiangmei Chen6Lisheng Zhang7College of Veterinary Medicine/Bio‐medical Center Huazhong Agricultural University Wuhan Hubei 430070 ChinaCollege of Veterinary Medicine/Bio‐medical Center Huazhong Agricultural University Wuhan Hubei 430070 ChinaCollege of Veterinary Medicine/Bio‐medical Center Huazhong Agricultural University Wuhan Hubei 430070 ChinaCollege of Veterinary Medicine/Bio‐medical Center Huazhong Agricultural University Wuhan Hubei 430070 ChinaCollege of Veterinary Medicine/Bio‐medical Center Huazhong Agricultural University Wuhan Hubei 430070 ChinaDepartment of Nephrology Chinese PLA General Hospital Chinese PLA Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases 28th Fuxing Road Beijing 100853 ChinaDepartment of Nephrology Chinese PLA General Hospital Chinese PLA Institute of Nephrology State Key Laboratory of Kidney Diseases National Clinical Research Center for Kidney Diseases 28th Fuxing Road Beijing 100853 ChinaCollege of Veterinary Medicine/Bio‐medical Center Huazhong Agricultural University Wuhan Hubei 430070 ChinaAbstract Male‐specific lethal 1 (MSL1) is critical for the formation of MSL histone acetyltransferase complex which acetylates histone H4 Lys16 (H4K16ac) to activate gene expression. However, the role of MSL1 in liver regeneration is poorly understood. Here, this work identifies MSL1 as a key regulator of STAT3 and histone H4 (H4) in hepatocytes. MSL1 forms condensates with STAT3 or H4 through liquid–liquid phase separation to enrich acetyl‐coenzyme A (Ac‐CoA), and Ac‐CoA in turn enhances MSL1 condensate formation, synergetically promoting the acetylation of STAT3 K685 and H4K16, thus stimulating liver regeneration after partial hepatectomy (PH). Additionally, increasing Ac‐CoA level can enhance STAT3 and H4 acetylation, thus promoting liver regeneration in aged mice. The results demonstrate that MSL1 condensate‐mediated STAT3 and H4 acetylation play an important role in liver regeneration. Thus, promoting the phase separation of MSL1 and increasing Ac‐CoA level may be a novel therapeutic strategy for acute liver diseases and transplantation.https://doi.org/10.1002/advs.202301094acetyl coenzyme Ahistone H4liquid–liquid phase separationliver regenerationMSL1STAT3 |
| spellingShingle | Yucheng He Shichao Wang Shenghui Liu Dan Qin Zhangmei Liu Liqiang Wang Xiangmei Chen Lisheng Zhang MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation Advanced Science acetyl coenzyme A histone H4 liquid–liquid phase separation liver regeneration MSL1 STAT3 |
| title | MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation |
| title_full | MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation |
| title_fullStr | MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation |
| title_full_unstemmed | MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation |
| title_short | MSL1 Promotes Liver Regeneration by Driving Phase Separation of STAT3 and Histone H4 and Enhancing Their Acetylation |
| title_sort | msl1 promotes liver regeneration by driving phase separation of stat3 and histone h4 and enhancing their acetylation |
| topic | acetyl coenzyme A histone H4 liquid–liquid phase separation liver regeneration MSL1 STAT3 |
| url | https://doi.org/10.1002/advs.202301094 |
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