The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression

Autor: Whittaker, Danielle E., Riegman, Kimberley L.H., Kasah, Sahrunizam, Mohan, Conor, Yu, Tian, Sala, Blanca Pijuan, Hebaishi, Husam, Caruso, Angela, Marques, Ana Claudia, Michetti, Caterina, Smachetti, María Eugenia Sanz, Shah, Apar, Sabbioni, Mara, Kulhanci, Omer, Tee, Wee-Wei, Reinberg, Danny, Scattoni, Maria Luisa, Volk, Holger, McGonnell, Imelda, Wardle, Fiona C., Fernandes, Cathy, Basson, M. Albert
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: The Journal of Clinical Investigation
CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Journal of Clinical Investigation
The Journal of clinical investigation, vol. 127, no. 3, pp. 874-887
Whittaker, D E, Riegman, K L H, Kasah, S, Mohan, C, Yu, T, Sala, B P, Hebaishi, H, Caruso, A, Marques, A C, Michetti, C, Smachetti, M E S, Shah, A, Sabbioni, M, Kulhanci, O, Tee, W W, Reinberg, D, Scattoni, M L, Volk, H, McGonnell, I, Wardle, F C, Fernandes, C & Basson, M A 2017, ' The chromatin remodeling factor CHD7 controls cerebellar development by regulating reelin expression ', Journal of Clinical Investigation, vol. 127, no. 3, pp. 874-887 . https://doi.org/10.1172/JCI83408
DOI: 10.1172/JCI83408
Popis: The mechanisms underlying the neurodevelopmental deficits associated with CHARGE syndrome, which include cerebellar hypoplasia, developmental delay, coordination problems, and autistic features, have not been identified. CHARGE syndrome has been associated with mutations in the gene encoding the ATP-dependent chromatin remodeler CHD7. CHD7 is expressed in neural stem and progenitor cells, but its role in neurogenesis during brain development remains unknown. Here we have shown that deletion of Chd7 from cerebellar granule cell progenitors (GCps) results in reduced GCp proliferation, cerebellar hypoplasia, developmental delay, and motor deficits in mice. Genome-wide expression profiling revealed downregulated expression of the gene encoding the glycoprotein reelin (Reln) in Chd7-deficient GCps. Recessive RELN mutations have been associated with severe cerebellar hypoplasia in humans. We found molecular and genetic evidence that reductions in Reln expression contribute to GCp proliferative defects and cerebellar hypoplasia in GCp-specific Chd7 mouse mutants. Finally, we showed that CHD7 is necessary for maintaining an open, accessible chromatin state at the Reln locus. Taken together, this study shows that Reln gene expression is regulated by chromatin remodeling, identifies CHD7 as a previously unrecognized upstream regulator of Reln, and provides direct in vivo evidence that a mammalian CHD protein can control brain development by modulating chromatin accessibility in neuronal progenitors. Fil: Whittaker, Danielle E.. Royal Veterinary College University Of London; . King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido Fil: Riegman, Kimberley L. H.. King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido Fil: Kasah, Sahrunizam. King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido Fil: Mohan, Conor. King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido Fil: Yu, Tian. King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido Fil: Sala, Blanca Pijuan. King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido Fil: Hebaishi, Husam. University College London; Estados Unidos Fil: Caruso, Angela. Istituto Superiore di Sanità. Department of Cell Biology and Neuroscience. Neurotoxicology and Neuroendocrinology Section; Italia Fil: Marques, Ana Claudia. University of Oxford. Department of Physiology, Anatomy and Genetics; Reino Unido Fil: Michetti, Caterina. Istituto Superiore di Sanità. Department of Cell Biology and Neuroscience. Neurotoxicology and Neuroendocrinology Section; Italia Fil: Sanz Smachetti, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones En Biodiversidad y Biotecnología; Argentina. Fundación para Investigaciones Biológicas Aplicadas; Argentina Fil: Shah, Apar. King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido Fil: Sabbioni, Mara. Istituto Superiore di Sanità. Department of Cell Biology and Neuroscience. Neurotoxicology and Neuroendocrinology Section; Italia Fil: Kulhanci, Omer. King’s College London, London, United Kingdom. Institute of Psychiatry, Psychology & Neuroscience. MRC Social, Genetic & Developmental Psychiatry Centre; Reino Unido Fil: Tee, Wee-Wei. New York University School of Medicine. Department of Molecular Pharmacology and Biochemistry. Howard Hughes Medical Institute; Estados Unidos Fil: Reinberg, Danny. New York University School of Medicine. Department of Molecular Pharmacology and Biochemistry. Howard Hughes Medical Institute; Estados Unidos Fil: Scattoni, Maria Luisa. Istituto Superiore di Sanità. Department of Cell Biology and Neuroscience. Neurotoxicology and Neuroendocrinology Section; Italia Fil: Volk, Holger. Royal Veterinary College University Of London; Reino Unido Fil: McGonnell, Imelda. Royal Veterinary College University Of London; Reino Unido Fil: Wardle, Fiona C.. King’s College London. Randall Division; Reino Unido Fil: Fernandez, Cathy. King’s College London, London, United Kingdom. Psychology & Neuroscience; Reino Unido Fil: Basson, Albert. King’s College London. Department of Craniofacial Development and Stem Cell Biology. Guy’s Hospital Tower Wing; Reino Unido
Databáze: OpenAIRE
Externí odkaz: