[en] While the cohesin complex is a key player in genome architecture, how it localizes to specific chromatin sites is not understood. Recently, we and others have proposed that direct interactions with transcription factors lead to the localization of the cohesin-loader complex (NIPBL/MAU2) within enhancers. Here, we identify two clusters of LxxLL motifs within the NIPBL sequence that regulate NIPBL dynamics, interactome, and NIPBL-dependent transcriptional programs. One of these clusters interacts with MAU2 and is necessary for the maintenance of the NIPBL-MAU2 heterodimer. The second cluster binds specifically to the ligand-binding domains of steroid receptors. For the glucocorticoid receptor (GR), we examine in detail its interaction surfaces with NIPBL and MAU2. Using AlphaFold2 and molecular docking algorithms, we uncover a GR-NIPBL-MAU2 ternary complex and describe its importance in GR-dependent gene regulation. Finally, we show that multiple transcription factors interact with NIPBL-MAU2, likely using interfaces other than those characterized for GR.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Fettweis, Grégory ; Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales ; Co-First authors
Wagh, Kaustubh ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA ; Co-First authors
Stavreva, Diana A ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA ; Co-First authors
Jiménez-Panizo, Alba ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA ; Instituto de Ciencias de la Vid y del Vino (ICVV), CSIC - Universidad de La Rioja - Gobierno de La Rioja, 26007 Logroño, Spain ; Co-First authors
Kim, Sohyoung ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Lion, Michelle ; Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Alegre-Martí, Andrea ; Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona (UB), 08028 Barcelona, Spain ; Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona (UB), 08028 Barcelona, Spain
Johnson, Thomas A; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Ball, David A ; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Karpova, Tatiana S; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Upadhyaya, Arpita ; Department of Physics, University of Maryland, College Park, Maryland 20742, USA ; Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA
Vertommen, Didier ; de Duve Institute, Université Catholique de Louvain, 1348 Louvain-la-Neuve, Belgium
Recio, Juan Fernández; Instituto de Ciencias de la Vid y del Vino (ICVV), CSIC - Universidad de La Rioja - Gobierno de La Rioja, 26007 Logroño, Spain
Estébanez-Perpiñá, Eva ; Institute of Biomedicine of the University of Barcelona (IBUB), University of Barcelona (UB), 08028 Barcelona, Spain ; Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona (UB), 08028 Barcelona, Spain
Dequiedt, Franck ; Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Hager, Gordon L; Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA ; Lead contact
