Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome
Copyright policy )Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome
Cornelia de Lange Syndrome (CdLS) is a genetic disorder linked to mutations in cohesin and its regulators. To date, it is unclear which function of cohesin is more relevant to the pathology of the syndrome. A mouse heterozygous for the gene encoding the cohesin loader Nipbl recapitulates many features of CdLS. We have carefully examined Nipbl deficient cells and here report that they have robust cohesion all along the chromosome. DNA replication, DNA repair and chromosome segregation are carried out efficiently in these cells. While bulk cohesin loading is unperturbed, binding to certain promoters such as the Protocadherin genes in brain is notably affected and alters gene expression. These results provide further support for the idea that developmental defects in CdLS are caused by deregulated transcription and not by malfunction of cohesion-related processes.
- University of California, San Francisco United States
- Department of Anatomy and Neurobiology United States
- University of California, Irvine United States
- Spanish National Cancer Research Centre Spain
DNA Repair, Chromosomal Proteins, Non-Histone, Messenger, Fluorescent Antibody Technique, Cell Cycle Proteins, Nibpl, Congenital, Mice, Chromosome Segregation, De Lange Syndrome, 2.1 Biological and endogenous factors, In Situ Hybridization, Cells, Cultured, In Situ Hybridization, Fluorescence, Pediatric, Cohesin, Mice, Knockout, Cultured, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Brain, Biological Sciences, Chromosomal Proteins, Physical sciences, Biological sciences, Phenotype, Embryo, Physical Sciences, Molecular Medicine, Western, Transcription, DNA Replication, 570, Heterozygote, Cell Survival, Intellectual and Developmental Disabilities (IDD), 1.1 Normal biological development and functioning, Cells, Knockout, Blotting, Western, 610, Real-Time Polymerase Chain Reaction, Fluorescence, Mouse model, Promoter Regions, Rare Diseases, Genetic, Genetics, Cornelia de Lange Syndrome, Animals, Cohesins, Molecular Biology, Animal, Mammalian, Neurosciences, Non-Histone, Fibroblasts, Embryo, Mammalian, Brain Disorders, Disease Models, Animal, Disease Models, RNA, Generic health relevance, Transcription Factors
DNA Repair, Chromosomal Proteins, Non-Histone, Messenger, Fluorescent Antibody Technique, Cell Cycle Proteins, Nibpl, Congenital, Mice, Chromosome Segregation, De Lange Syndrome, 2.1 Biological and endogenous factors, In Situ Hybridization, Cells, Cultured, In Situ Hybridization, Fluorescence, Pediatric, Cohesin, Mice, Knockout, Cultured, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Brain, Biological Sciences, Chromosomal Proteins, Physical sciences, Biological sciences, Phenotype, Embryo, Physical Sciences, Molecular Medicine, Western, Transcription, DNA Replication, 570, Heterozygote, Cell Survival, Intellectual and Developmental Disabilities (IDD), 1.1 Normal biological development and functioning, Cells, Knockout, Blotting, Western, 610, Real-Time Polymerase Chain Reaction, Fluorescence, Mouse model, Promoter Regions, Rare Diseases, Genetic, Genetics, Cornelia de Lange Syndrome, Animals, Cohesins, Molecular Biology, Animal, Mammalian, Neurosciences, Non-Histone, Fibroblasts, Embryo, Mammalian, Brain Disorders, Disease Models, Animal, Disease Models, RNA, Generic health relevance, Transcription Factors
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