Human gamma-satellite DNA maintains open chromatin structure and protects a transgene from epigenetic silencing.
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.
Kim
Jung-Hyun
JH
Laboratory of Molecular Pharmacology, National Cancer Institute, Bethesda, Maryland 20892, USA.
Ebersole
Thomas
T
Kouprina
Natalay
N
Noskov
Vladimir N
VN
Ohzeki
Jun-Ichirou
J
Masumoto
Hiroshi
H
Mravinac
Brankica
B
Sullivan
Beth A
BA
Pavlicek
Adam
A
Dovat
Sinisa
S
Pack
Svetlana D
SD
Kwon
Yoo-Wook
YW
Flanagan
Patrick T
PT
Loukinov
Dmitri
D
Lobanenkov
Victor
V
Larionov
Vladimir
V
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
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