Redundant and Specific Roles of Cohesin STAG Subunits in Chromatin Looping and Transcriptional Control
Downloaded from genome.cshlp.org on October 10, 2021 - Published by Cold Spring Harbor Laboratory Press Research Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcriptional control Valentina Casa,1,6 Macarena Moronta Gines,1,6 Eduardo Gade Gusmao,2,3,6 Johan A. Slotman,4 Anne Zirkel,2 Natasa Josipovic,2,3 Edwin Oole,5 Wilfred F.J. van IJcken,1,5 Adriaan B. Houtsmuller,4 Argyris Papantonis,2,3 and Kerstin S. Wendt1 1Department of Cell Biology, Erasmus MC, 3015 GD Rotterdam, The Netherlands; 2Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany; 3Institute of Pathology, University Medical Center, Georg-August University of Göttingen, 37075 Göttingen, Germany; 4Optical Imaging Centre, Erasmus MC, 3015 GD Rotterdam, The Netherlands; 5Center for Biomics, Erasmus MC, 3015 GD Rotterdam, The Netherlands 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 sub- units, 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 in- dividual binding sites and have distinct ways by which they affect looping and gene expression.
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