| Chromodomain proteins in development: lessons from CHARGE syndrome. | |
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MedLine Citation:
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PMID: 20507341 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In humans, heterozygous mutations in the adenosine triphosphate-dependent chromatin remodeling gene CHD7 cause CHARGE syndrome, a common cause of deaf-blindness, balance disorders, congenital heart malformations, and olfactory dysfunction with an estimated incidence of approximately 1 in 10,000 newborns. The clinical features of CHARGE in humans and mice are highly variable and incompletely penetrant, and most mutations appear to result in haploinsufficiency of functional CHD7 protein. Mice with heterozygous loss of function mutations in Chd7 are a good model for CHARGE syndrome, and analyses of mouse mutant phenotypes have begun to clarify a role for CHD7 during development and into adulthood. Chd7 heterozygous mutant mice have postnatal delayed growth, inner ear malformations, anosmia/hyposmia, and craniofacial defects, and Chd7 homozygous mutants are embryonic lethal. A central question in developmental biology is how chromodomain proteins like CHD7 regulate important developmental processes, and whether they directly activate or repress downstream gene transcription or act more globally to alter chromatin structure and/or function. CHD7 is expressed in a wide variety of tissues during development, suggesting that it has tissue-specific and developmental stage-specific roles. Here, we review recent and ongoing analyses of CHD7 function in mouse models and cell-based systems. These studies explore tissue-specific effects of CHD7 deficiency, known CHD7 interacting proteins, and downstream target sites for CHD7 binding. CHD7 is emerging as a critical regulator of important developmental processes in organs affected by human CHARGE syndrome. |
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Authors:
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W S Layman; E A Hurd; D M Martin |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review Date: 2010-04-08 |
Journal Detail:
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Title: Clinical genetics Volume: 78 ISSN: 1399-0004 ISO Abbreviation: Clin. Genet. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-05 Completed Date: 2010-10-19 Revised Date: 2011-09-12 |
Medline Journal Info:
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Nlm Unique ID: 0253664 Medline TA: Clin Genet Country: Denmark |
Other Details:
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Languages: eng Pagination: 11-20 Citation Subset: IM |
Affiliation:
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Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Abnormalities, Multiple Animals DNA Helicases / deficiency, physiology* DNA-Binding Proteins / deficiency, physiology* Deaf-Blind Disorders / physiopathology* Growth and Development Humans Mice Syndrome |
| Grant Support | |
ID/Acronym/Agency:
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R01 DC009410-01A1/DC/NIDCD NIH HHS; R01 DC009410-01A1S1/DC/NIDCD NIH HHS; R01 DC009410-02/DC/NIDCD NIH HHS; R01 DC009410-03/DC/NIDCD NIH HHS; R01 DC009410-04/DC/NIDCD NIH HHS; R01DC009410/DC/NIDCD NIH HHS; R01NS054784/NS/NINDS NIH HHS; T32DC00011/DC/NIDCD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chd7 protein, mouse; 0/DNA-Binding Proteins; EC 3.6.1.-/DNA Helicases; EC 5.99.-/CHD7 protein, human |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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