title: Epigenetic analysis of the critical region I for premature ovarian failure: demonstration of a highly heterochromatic domain on the long arm of the mammalian X chromosome.
abstract: BACKGROUND
  X chromosome rearrangements defined a critical region for premature ovarian failure (POF) that extended for >15 Mb in Xq. It has been shown previously that the region could be divided into two functionally distinct portions and suggested that balanced translocations interrupting its proximal part, critical region 1 (CR1), could be responsible for POF through downregulation of ovary expressed autosomal genes translocated to the X chromosome.
  
  
  CONCLUSIONS
  This study reports that such position effect can indeed be demonstrated by analysis of breakpoint regions in somatic cells of POF patients and by the finding that CR1 has a highly heterochromatic organisation, very different from that of the euchromatic autosomal regions involved in the rearrangements. The chromatin organisation of the POF CR1 is likely to be responsible for the epigenetic modifications observed in POF patients. The characteristics of CR1 and its downregulation in oocytes may very well explain its role in POF and the frequency of the POF phenotype in chromosomal rearrangements involving Xq. This study also demonstrates a large and evolutionary conserved domain of the long arm of the X chromosome, largely corresponding to CR1, that may have structural or functional roles, in oocyte maturation or in X chromosome inactivation.
authors.affiliation: DIBIT, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rizzolio
authors.forename: T
authors.initials: T
authors.lastname: Pramparo
authors.forename: C
authors.initials: C
authors.lastname: Sala
authors.forename: O
authors.initials: O
authors.lastname: Zuffardi
authors.forename: L
authors.initials: L
authors.lastname: De Santis
authors.forename: E
authors.initials: E
authors.lastname: Rabellotti
authors.forename: F
authors.initials: F
authors.lastname: Calzi
authors.forename: F
authors.initials: F
authors.lastname: Fusi
authors.forename: R
authors.initials: R
authors.lastname: Bellazzi
authors.forename: D
authors.initials: D
authors.lastname: Toniolo
mesh_terms: D000818:Animals; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D019457:Chromosome Breakage; D041321:Chromosomes, Human, X; D033481:Chromosomes, Mammalian; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D014178:Translocation, Genetic; D014960:X Chromosome
chemical_list: D006570:Heterochromatin; D006657:Histones