Linked Life Data

21427128

Source:http://linkedlifedata.com/resource/pubmed/id/21427128

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2011-5-10
pubmed:abstractText
X-linked ATR-X (alpha thalassemia, mental retardation, X-linked) syndrome in males is characterized by mental retardation, facial dysmorphism, alpha thalassemia and urogenital abnormalities, including small testes. It is unclear how mutations in the chromatin-remodeling protein ATRX cause these highly specific clinical features, since ATRX is widely expressed during organ development. To investigate the mechanisms underlying the testicular defects observed in ATR-X syndrome, we generated ScAtrxKO (Sertoli cell Atrx knockout) mice with Atrx specifically inactivated in the supporting cell lineage (Sertoli cells) of the mouse testis. ScAtrxKO mice developed small testes and discontinuous tubules, due to prolonged G2/M phase and apoptosis of proliferating Sertoli cells during fetal life. Apoptosis might be a consequence of the cell cycle defect. We also found that the onset of spermatogenesis was delayed in postnatal mice, with a range of spermatogenesis defects evident in adult ScAtrxKO mice. ATRX and the androgen receptor (AR) physically interact in the testis and in the Sertoli cell line TM4 and co-operatively activate the promoter of Rhox5, an important direct AR target. We also demonstrate that ATRX directly binds to the Rhox5 promoter in TM4 cells. Finally, gene expression of Rhox5 and of another AR-dependent gene, Spinlw1, was reduced in ScAtrxKO testes. These data suggest that ATRX can directly enhance the expression of androgen-dependent genes through physical interaction with AR. Recruitment of ATRX by DNA sequence-specific transcription factors could be a general mechanism by which ATRX achieves tissue-specific transcriptional regulation which could explain the highly specific clinical features of ATR-X syndrome when ATRX is mutated.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1460-2083
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2213-24
pubmed:dateRevised
2011-9-27
pubmed:meshHeading
pubmed-meshheading:21427128-Animals, pubmed-meshheading:21427128-Apoptosis, pubmed-meshheading:21427128-Cell Cycle, pubmed-meshheading:21427128-Cell Proliferation, pubmed-meshheading:21427128-Cells, Cultured, pubmed-meshheading:21427128-Chromatin Assembly and Disassembly, pubmed-meshheading:21427128-DNA Helicases, pubmed-meshheading:21427128-Disease Models, Animal, pubmed-meshheading:21427128-Female, pubmed-meshheading:21427128-Gene Expression Regulation, pubmed-meshheading:21427128-Homeodomain Proteins, pubmed-meshheading:21427128-Immunoprecipitation, pubmed-meshheading:21427128-Male, pubmed-meshheading:21427128-Mental Retardation, X-Linked, pubmed-meshheading:21427128-Mice, pubmed-meshheading:21427128-Mice, Inbred C57BL, pubmed-meshheading:21427128-Mice, Knockout, pubmed-meshheading:21427128-Mutation, pubmed-meshheading:21427128-Nuclear Proteins, pubmed-meshheading:21427128-Promoter Regions, Genetic, pubmed-meshheading:21427128-Receptors, Androgen, pubmed-meshheading:21427128-Sequence Analysis, DNA, pubmed-meshheading:21427128-Sertoli Cells, pubmed-meshheading:21427128-Testis, pubmed-meshheading:21427128-Transcription Factors, pubmed-meshheading:21427128-alpha-Thalassemia
pubmed:year
2011
pubmed:articleTitle
Defective survival of proliferating Sertoli cells and androgen receptor function in a mouse model of the ATR-X syndrome.
pubmed:affiliation
Molecular Genetics and Development Division, Prince Henry’s Institute of Medical Research, Clayton, VIC 3168, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't