The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands.

Autor:	Stielow B; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, 35043 Marburg, Germany., Zhou Y; Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China., Cao Y; Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China., Simon C; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, 35043 Marburg, Germany., Pogoda HM; Institute of Zoology, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Jiang J; Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China., Ren Y; Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China., Phanor SK; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Rohner I; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, 35043 Marburg, Germany., Nist A; Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University of Marburg, 35043 Marburg, Germany., Stiewe T; Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University of Marburg, 35043 Marburg, Germany., Hammerschmidt M; Institute of Zoology, University of Cologne, Cologne, Germany.; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany., Shi Y; Division of Newborn Medicine and Epigenetics Program, Department of Pediatrics, Boston Children's Hospital, Boston, Harvard Medical School, Boston, MA 02115, USA.; Ludwig Institute for Cancer Research, Oxford University, Oxford, UK., Bulyk ML; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Wang Z; Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China. robert.liefke@imt.uni-marburg.de wangz@bnu.edu.cn., Liefke R; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, 35043 Marburg, Germany. robert.liefke@imt.uni-marburg.de wangz@bnu.edu.cn.; Department of Hematology, Oncology and Immunology, University Hospital Giessen and Marburg, 35043 Marburg, Germany.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2021 May 12; Vol. 7 (20). Date of Electronic Publication: 2021 May 12 (Print Publication: 2021).
DOI:	10.1126/sciadv.abf2229
Abstrakt:	CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)
Databáze:	MEDLINE
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