It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Cornelia de Lange Syndrome (CdLS) is a human developmental disorder caused by mutations that compromise the function of cohesin, a major regulator of 3D genome organization. Cognitive impairment is a universal and as yet unexplained feature of CdLS. We characterize the transcriptional profile of cortical neurons from CdLS patients and find deregulation of hundreds of genes enriched for neuronal functions related to synaptic transmission, signalling processes, learning and behaviour. Inducible proteolytic cleavage of cohesin disrupts 3D genome organization and transcriptional control in post-mitotic cortical mouse neurons, demonstrating that cohesin is continuously required for neuronal gene expression. The genes affected by acute depletion of cohesin belong to similar gene ontology classes and show significant numerical overlap with genes deregulated in CdLS. Interestingly, reconstitution of cohesin function largely rescues altered gene expression, including the expression of genes deregulated in CdLS.
A feature of cohesin mutations in patients with Cornelia de Lange Syndrome (CdLS) is intellectual disability, but the underlying mechanisms have remained obscure. Here the authors show gene expression is deregulated in CdLS neurons and is recapitulated in a mouse model with cohesin depletion, which can be restored by re-expression of cohesin.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details






1 Imperial College London, Lymphocyte Development Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); University of Bonn, Institute of Innate Immunity, Bonn, Germany (GRID:grid.10388.32) (ISNI:0000 0001 2240 3300)
2 Imperial College London, Lymphocyte Development Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Research Institute of Molecular Pathology, Vienna, Austria (GRID:grid.14826.39) (ISNI:0000 0000 9799 657X)
3 Imperial College London, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
4 Imperial College London, Lymphocyte Development Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Imperial College London, Computational Regulatory Genomics Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
5 Imperial College London, Lymphocyte Development Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); Shanghai Jiao Tong University, School of Life Sciences and Biotechnology, Shanghai, China (GRID:grid.16821.3c) (ISNI:0000 0004 0368 8293)
6 Imperial College London, Computational Regulatory Genomics Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)
7 The Children’s Hospital of Philadelphia, Division of Human Genetics, The Department of Pediatrics, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770)
8 The Children’s Hospital of Philadelphia, Division of Human Genetics, The Department of Pediatrics, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770); The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, USA (GRID:grid.25879.31) (ISNI:0000 0004 1936 8972); The Children’s Hospital of Philadelphia, Department of Pathology and Laboratory Medicine, Philadelphia, USA (GRID:grid.239552.a) (ISNI:0000 0001 0680 8770)
9 Imperial College London, Computational Regulatory Genomics Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111); University of Bergen, Sars International Centre for Marine Molecular Biology, Bergen, Norway (GRID:grid.7914.b) (ISNI:0000 0004 1936 7443)
10 Imperial College London, Lymphocyte Development Group, Epigenetics Section, MRC London Institute of Medical Sciences, Institute of Clinical Sciences, Faculty of Medicine, London, UK (GRID:grid.7445.2) (ISNI:0000 0001 2113 8111)