TY - JOUR
T1 - Poly(ADP-ribosyl)ation regulates CTCF-dependent chromatin insulation
AU - Yu, Wenqiang
AU - Ginjala, Vasudeva
AU - Pant, Vinod
AU - Chernukhin, Igor
AU - Whitehead, Joanne
AU - Docquier, France
AU - Farrar, Dawn
AU - Tavoosidana, Gholamreza
AU - Mukhopadhyay, Rituparna
AU - Kanduri, Chandrasekhar
AU - Oshimura, Mitsuo
AU - Feinberg, Andrew P.
AU - Lobanenkov, Victor
AU - Klenova, Elena
AU - Ohlsson, Rolf
N1 - Funding Information:
We thank A. Mattsson for expert technical assistance, H. Smith and M. O’Farrell for help with the in vitro poly(ADP-ribosyl)ation assay, S. Shamsuddin for providing the domains of CTCF expressed in bacterial system, P. Hassa for helpful comments, A. Vostrov and W. Quitschke for the recombinant CTCF from Pichia and A. Isaksson and the Wallenberg microarray platform at the Rudbeck Laboratory for their assistance. This work was supported by the Swedish Science Research Council (V.R., R.O.), the Swedish Cancer Research Foundation (C.F., R.O.), the Swedish Pediatric Cancer Foundation (B.C.F., R.O.), the Lundberg Foundation (R.O.), the Wallenberg Foundation (R.O.), the Juvenile Diabetes Research Foundation International (R.O.), the Breast Cancer Campaign (F.D., E.K.), PhD Studentship from the University of Essex (D.F.), Research Promotion Fund from the University of Essex (I.C., F.D., E.K.) and the Association for International Cancer Research (I.C., E.K.).
PY - 2004/10
Y1 - 2004/10
N2 - 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-ribosyI)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.
AB - 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-ribosyI)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.
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U2 - 10.1038/ng1426
DO - 10.1038/ng1426
M3 - Article
C2 - 15361875
AN - SCOPUS:6944231017
SN - 1061-4036
VL - 36
SP - 1105
EP - 1110
JO - Nature Genetics
JF - Nature Genetics
IS - 10
ER -