Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation.
Chromatin insulators demarcate expression domains by blocking the cis effects of enhancers or silencers in a position-dependent manner. We show that the chromatin insulator protein CTCF carries a post-translational modification: poly(ADP-ribosyl)ation. Chromatin immunoprecipitation analysis showed that a poly(ADP-ribosyl)ation mark, which exclusively segregates with the maternal allele of the insulator domain in the H19 imprinting control region, requires the bases that are essential for interaction with CTCF. Chromatin immunoprecipitation-on-chip analysis documented that the link between CTCF and poly(ADP-ribosyl)ation extended to more than 140 mouse CTCF target sites. An insulator trap assay showed that the insulator function of most of these CTCF target sites is sensitive to 3-aminobenzamide, an inhibitor of poly(ADP-ribose) polymerase activity. We suggest that poly(ADP-ribosyl)ation imparts chromatin insulator properties to CTCF at both imprinted and nonimprinted loci, which has implications for the regulation of expression domains and their demise in pathological lesions.
Yu
Wenqiang
W
Department of Development & Genetics, Evolution Biology Centre, Uppsala University, Norbyvägen 18A, S-752 36 Uppsala, Sweden.
Ginjala
Vasudeva
V
Pant
Vinod
V
Chernukhin
Igor
I
Whitehead
Joanne
J
Docquier
France
F
Farrar
Dawn
D
Tavoosidana
Gholamreza
G
Mukhopadhyay
Rituparna
R
Kanduri
Chandrasekhar
C
Oshimura
Mitsuo
M
Feinberg
Andrew P
AP
Lobanenkov
Victor
V
Klenova
Elena
E
Ohlsson
Rolf
R
D000818:Animals; D000076246:CCCTC-Binding Factor; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012097:Repressor Proteins; D011064:Poly Adenosine Diphosphate Ribose; D007335:Insulin-Like Growth Factor II