Stielow, Bastian, Zhou, Yuqiao ORCID: 0000-0002-9597-7513, Cao, Yinghua, Simon, Clara ORCID: 0000-0002-0298-9858, Pogoda, Hans-Martin, Jiang, Junyi, Ren, Yanpeng, Phanor, Sabrina Keita, Rohner, Iris, Nist, Andrea, Stiewe, Thorsten ORCID: 0000-0003-0134-7826, Hammerschmidt, Matthias, Shi, Yang, Bulyk, Martha L., Wang, Zhanxin and Liefke, Robert ORCID: 0000-0002-8549-637X (2021). The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands. Sci. Adv., 7 (20). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 2375-2548

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Stielow, BastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhou, YuqiaoUNSPECIFIEDorcid.org/0000-0002-9597-7513UNSPECIFIED
Cao, YinghuaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simon, ClaraUNSPECIFIEDorcid.org/0000-0002-0298-9858UNSPECIFIED
Pogoda, Hans-MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jiang, JunyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ren, YanpengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phanor, Sabrina KeitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rohner, IrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nist, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stiewe, ThorstenUNSPECIFIEDorcid.org/0000-0003-0134-7826UNSPECIFIED
Hammerschmidt, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shi, YangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bulyk, Martha L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, ZhanxinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liefke, RobertUNSPECIFIEDorcid.org/0000-0002-8549-637XUNSPECIFIED
URN: urn:nbn:de:hbz:38-599016
DOI: 10.1126/sciadv.abf2229
Journal or Publication Title: Sci. Adv.
Volume: 7
Number: 20
Date: 2021
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 2375-2548
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BINDING PROTEIN; CXXC DOMAIN; DNA; EXPRESSION; ELEMENTS; LSD1; POLYMERIZATION; ULTRAFAST; ALIGNMENT; COMPLEXMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59901

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