title: Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing.
abstract: The role of repetitive DNA sequences in pericentromeric regions with respect to kinetochore/heterochromatin structure and function is poorly understood. Here, we use a mouse erythroleukemia cell (MEL) system for studying how repetitive DNA assumes or is assembled into different chromatin structures. We show that human gamma-satellite DNA arrays allow a transcriptionally permissive chromatin conformation in an adjacent transgene and efficiently protect it from epigenetic silencing. These arrays contain CTCF and Ikaros binding sites. In MEL cells, this gamma-satellite DNA activity depends on binding of Ikaros proteins involved in differentiation along the hematopoietic pathway. Given our discovery of gamma-satellite DNA in pericentromeric regions of most human chromosomes and a dynamic chromatin state of gamma-satellite arrays in their natural location, we suggest that gamma-satellite DNA represents a unique region of the functional centromere with a possible role in preventing heterochromatin spreading beyond the pericentromeric region.
authors.affiliation: Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Thomas
authors.initials: T
authors.lastname: Ebersole
authors.forename: Natalay
authors.initials: N
authors.lastname: Kouprina
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Noskov
authors.forename: Jun-Ichirou
authors.initials: J
authors.lastname: Ohzeki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Masumoto
authors.forename: Brankica
authors.initials: B
authors.lastname: Mravinac
authors.forename: Beth A
authors.initials: BA
authors.lastname: Sullivan
authors.forename: Adam
authors.initials: A
authors.lastname: Pavlicek
authors.forename: Sinisa
authors.initials: S
authors.lastname: Dovat
authors.forename: Svetlana D
authors.initials: SD
authors.lastname: Pack
authors.forename: Yoo-Wook
authors.initials: YW
authors.lastname: Kwon
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Flanagan
authors.forename: Dmitri
authors.initials: D
authors.lastname: Loukinov
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
authors.forename: Vladimir
authors.initials: V
authors.lastname: Larionov
mesh_terms: D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002503:Centromere / Q000235:genetics; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D002877:Chromosomes, Human / Q000235:genetics; D004276:DNA, Satellite / Q000737:chemistry / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D005822:Genetic Vectors; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics / Q000378:metabolism; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019076:Transgenes / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D051740:Ikaros Transcription Factor; D008156:Luciferases