title: The multi zinc-finger protein Trps1 acts as a regulator of histone deacetylation during mitosis.
abstract: TRPS1, the gene mutated in human "Tricho-Rhino-Phalangeal syndrome," encodes a multi zinc-finger nuclear regulator of chondrocyte proliferation and differentiation. Here, we have identified a new function of Trps1 in controlling mitotic progression in chondrocytes. Loss of Trps1 in mice leads to an increased proportion of cells arrested in mitosis and, subsequently, to chromosome segregation defects. Searching for the molecular basis of the defect, we found that Trps1 acts as regulator of histone deacetylation. Trps1 interacts with two histone deacetylases, Hdac1 and Hdac4, thereby increasing their activity. Loss of Trps1 results in histone H3 hyperacetylation, which is maintained during mitosis. Consequently, chromatin condensation and binding of HP1 is impaired, and Trps1-deficient chondrocytes accumulate in prometaphase. Overexpression of Hdac4 rescues the mitotic defect of Trps1-deficient chondrocytes, identifying Trps1 as an important regulator of chromatin deacetylation during mitosis in chondrocytes. Our data provide the first evidence that the control of mitosis can be linked to the regulation of chondrocyte differentiation by epigenetic consequences of altered Hdac activity.
authors.affiliation: Center for Medical Biotechnology, Department of Developmental Biology, University Duisburg-Essen, Essen, Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Wuelling
authors.forename: Markus
authors.initials: M
authors.lastname: Pasdziernik
authors.forename: Carina N
authors.initials: CN
authors.lastname: Moll
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Thiesen
authors.forename: Sabine
authors.initials: S
authors.lastname: Schneider
authors.forename: Christian
authors.initials: C
authors.lastname: Johannes
authors.forename: Andrea
authors.initials: A
authors.lastname: Vortkamp
mesh_terms: D000818:Animals; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D044127:Epigenesis, Genetic; D050980:GATA Transcription Factors / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics*; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics* / Q000378:metabolism; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D061251:Primary Cell Culture; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D015398:Signal Transduction
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D050980:GATA Transcription Factors; D006657:Histones; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C525953:Trps1 protein, mouse; C484389:Hdac1 protein, mouse; C498618:Hdac5 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases
keywords: Hdac activity; Trps1; cell cycle; chondrocyte mitosis; chromosome segregate; histone deacetylase; hyperacetylaeted chromatin; mitotic prgression
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