Active and repressive chromatin are interspersed without spreading in an imprinted gene cluster in the mammalian genome.
The Igf2r imprinted cluster is an epigenetic silencing model in which expression of a ncRNA silences multiple genes in cis. Here, we map a 250 kb region in mouse embryonic fibroblast cells to show that histone modifications associated with expressed and silent genes are mutually exclusive and localized to discrete regions. Expressed genes were modified at promoter regions by H3K4me3 + H3K4me2 + H3K9Ac and on putative regulatory elements flanking active promoters by H3K4me2 + H3K9Ac. Silent genes showed two types of nonoverlapping profile. One type spread over large domains of tissue-specific silent genes and contained H3K27me3 alone. A second type formed localized foci on silent imprinted gene promoters and a nonexpressed pseudogene and contained H3K9me3 + H4K20me3 +/- HP1. Thus, mammalian chromosome arms contain active chromatin interspersed with repressive chromatin resembling the type of heterochromatin previously considered a feature of centromeres, telomeres, and the inactive X chromosome.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Institute of Genetics, Max F. Perutz Laboratories, Vienna Biocenter, Dr. Bohr-Gasse 9/4, A-1030 Vienna, Austria.
Kakkad
K
Regha
Mathew A
MA
Sloane
Ru
R
Huang
Florian M
FM
Pauler
Katarzyna E
KE
Warczok
Balázs
B
Melikant
Martin
M
Radolf
Joost H A
JH
Martens
Gunnar
G
Schotta
Thomas
T
Jenuwein
Denise P
DP
Barlow
D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002875:Chromosomes; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D020868:Gene Silencing; D016678:Genome; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D020161:Physical Chromosome Mapping
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones