CTCF binding and higher order chromatin structure of the H19 locus are maintained in mitotic chromatin.
Most of the transcription factors, RNA polymerases and enhancer binding factors are absent from condensed mitotic chromosomes. In contrast, epigenetic marks of active and inactive genes somehow survive mitosis, since the activity status from one cell generation to the next is maintained. For the zinc-finger protein CTCF, a role in interpreting and propagating epigenetic states and in separating expression domains has been documented. To test whether such a domain structure is preserved during mitosis, we examined whether CTCF is bound to mitotic chromatin. Here we show that in contrast to other zinc-finger proteins, CTCF indeed is bound to mitotic chromosomes. Mitotic binding is mediated by a portion of the zinc-finger DNA binding domain and involves sequence specific binding to target sites. Furthermore, the chromatin loop organized by the CTCF-bound, differentially methylated region at the Igf2/H19 locus can be detected in mitosis. In contrast, the enhancer/promoter loop of the same locus is lost in mitosis. This may provide a novel form of epigenetic memory during cell division.
Burke
Les J
LJ
Institute for Genetics, Justus-Liebig-Universitaet Giessen, Giessen, Germany.
Zhang
Ru
R
Bartkuhn
Marek
M
Tiwari
Vijay K
VK
Tavoosidana
Gholamreza
G
Kurukuti
Sreenivasulu
S
Weth
Christine
C
Leers
Joerg
J
Galjart
Niels
N
Ohlsson
Rolf
R
Renkawitz
Rainer
R
D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008938:Mitosis; D008968:Molecular Conformation; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D016335:Zinc Fingers
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D000090266:Chromobox Protein Homolog 5