title: Epigenetic modifications and chromosome conformations of the beta globin locus throughout development.
abstract: Human embryonic stem cells provide an alternative to using human embryos for studying developmentally regulated gene expression. The co-expression of high levels of embryonic ε and fetal γ globin by the hESC-derived erythroblasts allows the interrogation of ε globin regulation at the transcriptional and epigenetic level which could only be attained previously by studying cell lines or transgenic mice. In this study, we compared the histone modifications across the β globin locus of the undifferentiated hESCs and hESC-, FL-, and mobilized PB CD34(+) cells-derived erythroblasts, which have distinct globin expression patterns corresponding to their developmental stages. We demonstrated that the histone codes employed by the β globin locus are conserved throughout development. Furthermore, in spite of the close proximity of the ε globin promoter, as compared to the β or γ globin promoter, with the LCR, a chromatin loop was also formed between the LCR and the active ε globin promoter, similar to the loop that forms between the β or γ globin promoters and the LCR, in contrary to the previously proposed tracking mechanism.
authors.affiliation: Department of Medicine, Division of Hematology, University of Washington, NE Pacific St, Box 357710, Seattle, WA 98195, USA.
authors.forename: Kai-Hsin
authors.initials: KH
authors.lastname: Chang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Andy
authors.initials: A
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: Cao
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yang
authors.forename: Halvard
authors.initials: H
authors.lastname: Bonig
authors.forename: John A
authors.initials: JA
authors.lastname: Stamatoyannopoulos
authors.forename: Thalia
authors.initials: T
authors.lastname: Papayannopoulou
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D033481:Chromosomes, Mammalian / Q000235:genetics*; D047108:Embryonic Development / Q000235:genetics*; D044127:Epigenesis, Genetic; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci / Q000235:genetics*; D006801:Humans; D019901:Locus Control Region / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism
chemical_list: D055544:beta-Globins