MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells

Summary: Polycomb repressive complex 1.6 (PRC1.6), one of the PRC1 subtypes, plays crucial roles in preventing the ectopic expression of meiosis-related genes in mouse embryonic stem cells (ESCs). In addition to the histone modifications H2AK119ub1 and H3K27me3 that are deposited by PRC1 and PRC2, r...

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Main Authors: Kousuke Uranishi, Masataka Hirasaki, Masazumi Nishimoto, Robert J. Klose, Akihiko Okuda, Ayumu Suzuki
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225013203
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author Kousuke Uranishi
Masataka Hirasaki
Masazumi Nishimoto
Robert J. Klose
Akihiko Okuda
Ayumu Suzuki
author_facet Kousuke Uranishi
Masataka Hirasaki
Masazumi Nishimoto
Robert J. Klose
Akihiko Okuda
Ayumu Suzuki
author_sort Kousuke Uranishi
collection DOAJ
description Summary: Polycomb repressive complex 1.6 (PRC1.6), one of the PRC1 subtypes, plays crucial roles in preventing the ectopic expression of meiosis-related genes in mouse embryonic stem cells (ESCs). In addition to the histone modifications H2AK119ub1 and H3K27me3 that are deposited by PRC1 and PRC2, respectively, many meiosis-related genes bear the trimethylated lysine 9 of histone H3 (H3K9me3) mark in ESCs. However, the precise molecular mechanisms that deposit this mark on these genes in ESCs remain unknown. Here, we demonstrated that MGA, a scaffolding component of PRC1.6, is directly involved in recruiting SETDB1, an enzyme that catalyzes this histone modification, via its interaction with ATF7IP. Thus, our findings indicate that MGA plays a dual role, first being central in establishing a PRC1/PRC2-dependent repressive state by contributing to the construction of PRC1.6 as a scaffolding component, and then inducing a more robustly repressed state by recruiting the STEDB1/ATF7IP complex for H3K9me3 modification.
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institution Matheson Library
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spelling doaj-art-af4639f2dea640cf99a444e4ed19e09f2025-07-19T04:38:45ZengElsevieriScience2589-00422025-08-01288113059MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cellsKousuke Uranishi0Masataka Hirasaki1Masazumi Nishimoto2Robert J. Klose3Akihiko Okuda4Ayumu Suzuki5Division of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama 350-1241, Japan; Department of Clinical Cancer Genomics, International Medical Center, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama 350-1241, JapanDivision of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama 350-1241, Japan; Department of Clinical Cancer Genomics, International Medical Center, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama 350-1241, JapanDivision of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama 350-1241, Japan; Biomedical Research Center, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, JapanDepartment of Biochemistry, University of Oxford, Oxford OX1 3QU, UKDivision of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama 350-1241, Japan; Corresponding authorDivision of Biomedical Sciences, Research Center for Genomic Medicine, Saitama Medical University, 1397-1 Yamane Hidaka, Saitama 350-1241, Japan; Laboratory Animal Resource Center in Trans-Border Medical Research Center, Institute of Medicine, University of Tsukuba, 1-1-1 Tennoudai, Itsukuba, Ibaraki 305-8575, Japan; Corresponding authorSummary: Polycomb repressive complex 1.6 (PRC1.6), one of the PRC1 subtypes, plays crucial roles in preventing the ectopic expression of meiosis-related genes in mouse embryonic stem cells (ESCs). In addition to the histone modifications H2AK119ub1 and H3K27me3 that are deposited by PRC1 and PRC2, respectively, many meiosis-related genes bear the trimethylated lysine 9 of histone H3 (H3K9me3) mark in ESCs. However, the precise molecular mechanisms that deposit this mark on these genes in ESCs remain unknown. Here, we demonstrated that MGA, a scaffolding component of PRC1.6, is directly involved in recruiting SETDB1, an enzyme that catalyzes this histone modification, via its interaction with ATF7IP. Thus, our findings indicate that MGA plays a dual role, first being central in establishing a PRC1/PRC2-dependent repressive state by contributing to the construction of PRC1.6 as a scaffolding component, and then inducing a more robustly repressed state by recruiting the STEDB1/ATF7IP complex for H3K9me3 modification.http://www.sciencedirect.com/science/article/pii/S2589004225013203BiochemistryCell biologyStem cells research
spellingShingle Kousuke Uranishi
Masataka Hirasaki
Masazumi Nishimoto
Robert J. Klose
Akihiko Okuda
Ayumu Suzuki
MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells
iScience
Biochemistry
Cell biology
Stem cells research
title MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells
title_full MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells
title_fullStr MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells
title_full_unstemmed MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells
title_short MGA directly recruits SETDB1/ATF7IP for histone H3K9me3 mark on meiosis-related genes in mouse embryonic stem cells
title_sort mga directly recruits setdb1 atf7ip for histone h3k9me3 mark on meiosis related genes in mouse embryonic stem cells
topic Biochemistry
Cell biology
Stem cells research
url http://www.sciencedirect.com/science/article/pii/S2589004225013203
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