Universität zu Köln

Casa, Valentina, Gines, Macarena Moronta, Gusmao, Eduardo, Slotman, Johan A. ORCID: 0000-0001-9705-9620, Zirkel, Anne, Josipovic, Natasa, Oole, Edwin, van IJcken, Wilfred F. J., Houtsmuller, Adriaan B., Papantonis, Argyris and Wendt, Kerstin S. (2020). Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcriptional control. Genome Res., 30 (4). S. 515 - 528. COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. ISSN 1549-5469

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Abstract

Cohesin is a ring-shaped multiprotein complex that is crucial for 3D genome organization and transcriptional regulation during differentiation and development. It also confers sister chromatid cohesion and facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A, and RAD21, cohesin in somatic cells contains one of two orthologous STAG subunits, STAG1 or STAG2. How these variable subunits affect the function of the cohesin complex is still unclear. STAG1- and STAG2-cohesin were initially proposed to organize cohesion at telomeres and centromeres, respectively. Here, we uncover redundant and specific roles of STAG1 and STAG2 in gene regulation and chromatin looping using HCT116 cells with an auxin-inducible degron (AID) tag fused to either STAG1 or STAG2. Following rapid depletion of either subunit, we perform high-resolution Hi-C, gene expression, and sequential ChIP studies to show that STAG1 and STAG2 do not co-occupy individual binding sites and have distinct ways by which they affect looping and gene expression. These findings are further supported by single-molecule localizations via direct stochastic optical reconstruction microscopy (dSTORM) super-resolution imaging. Since somatic and congenital mutations of the STAG subunits are associated with cancer (STAG2) and intellectual disability syndromes with congenital abnormalities (STAG1 and STAG2), we verified STAG1-/STAG2-dependencies using human neural stem cells, hence highlighting their importance in particular disease contexts.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Casa, Valentina UNSPECIFIED UNSPECIFIED UNSPECIFIED Gines, Macarena Moronta UNSPECIFIED UNSPECIFIED UNSPECIFIED Gusmao, Eduardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Slotman, Johan A. UNSPECIFIED orcid.org/0000-0001-9705-9620 UNSPECIFIED Zirkel, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Josipovic, Natasa UNSPECIFIED UNSPECIFIED UNSPECIFIED Oole, Edwin UNSPECIFIED UNSPECIFIED UNSPECIFIED van IJcken, Wilfred F. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Houtsmuller, Adriaan B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Papantonis, Argyris UNSPECIFIED UNSPECIFIED UNSPECIFIED Wendt, Kerstin S. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-338615
DOI:	10.1101/gr.253211.119
Journal or Publication Title:	Genome Res.
Volume:	30
Number:	4
Page Range:	S. 515 - 528
Date:	2020
Publisher:	COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Place of Publication:	COLD SPRING HARBOR
ISSN:	1549-5469
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MAMMALIAN GENOMES; GENE-EXPRESSION; CTCF; MUTATIONS; IDENTIFICATION; INACTIVATION; ORGANIZATION; DEGRADATION; INSULATION; GENERATION Multiple languages Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/33861