Universität zu Köln

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

Full text not available from this repository.

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:	Creators Email ORCID ORCID Put Code Stielow, Bastian UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhou, Yuqiao UNSPECIFIED orcid.org/0000-0002-9597-7513 UNSPECIFIED Cao, Yinghua UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Clara UNSPECIFIED orcid.org/0000-0002-0298-9858 UNSPECIFIED Pogoda, Hans-Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Jiang, Junyi UNSPECIFIED UNSPECIFIED UNSPECIFIED Ren, Yanpeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Phanor, Sabrina Keita UNSPECIFIED UNSPECIFIED UNSPECIFIED Rohner, Iris UNSPECIFIED UNSPECIFIED UNSPECIFIED Nist, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Stiewe, Thorsten UNSPECIFIED orcid.org/0000-0003-0134-7826 UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED Shi, Yang UNSPECIFIED UNSPECIFIED UNSPECIFIED Bulyk, Martha L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Zhanxin UNSPECIFIED UNSPECIFIED UNSPECIFIED Liefke, Robert UNSPECIFIED orcid.org/0000-0002-8549-637X UNSPECIFIED
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:	Keywords Language BINDING PROTEIN; CXXC DOMAIN; DNA; EXPRESSION; ELEMENTS; LSD1; POLYMERIZATION; ULTRAFAST; ALIGNMENT; COMPLEX Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59901