ENHANCER-BLOCKING ACTIVITY;
MAMMARY EPITHELIAL-CELLS;
DNA METHYLATION;
PROMOTER METHYLATION;
BREAST-CANCER;
PROTEIN CTCF;
LUNG-CANCER;
HYPERMETHYLATION;
EXPRESSION;
GENE;
D O I:
10.1016/j.molcel.2009.04.001
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
The p16(INK4a) tumor suppressor gene is a frequent target of epigenetic inactivation in human cancers, which is an early event in breast carcinogenesis. We describe the existence of a chromatin boundary upstream of the p16 gene that is lost when this gene is aberrantly silenced. We show that the multifunctional protein CTCF associates in the vicinity of this boundary and absence of binding strongly coincides with p16 silencing in multiple types of cancer cells. CTCF binding also correlates with RASSF1A and CDH1 gene activation, and CTCF interaction is absent when these genes are methylated and silenced. Interestingly, defective poly(ADP-ribosyl)ation of CTCF and dissociation from the molecular chaperone Nucleolin occur in p 16-silenced cells, abrogating its proper function. Thus, destabilization of specific chromosomal boundaries through aberrant crosstalk between CTCF, poly(ADP-ribosyl)ation, and DNA methylation may be a general mechanism to inactivate tumor suppressor genes and initiate tumorigenesis in numerous forms of human cancers.
机构:
Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USAUniv N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA
Klose, Robert J.
Yi Zhang
论文数: 0引用数: 0
h-index: 0
机构:
Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USAUniv N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Ling, JQ
Li, T
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Li, T
Hu, JF
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Hu, JF
Vu, TH
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Vu, TH
Chen, HL
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Chen, HL
Qiu, XW
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Qiu, XW
Cherry, AM
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Cherry, AM
Hoffman, AR
论文数: 0引用数: 0
h-index: 0
机构:
Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USAPalo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Ng, MHL
Chung, YF
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Chung, YF
Lo, KW
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Lo, KW
Wickham, NWR
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Wickham, NWR
Lee, JCK
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Lee, JCK
Huang, DP
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
机构:
Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USAUniv N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA
Klose, Robert J.
Yi Zhang
论文数: 0引用数: 0
h-index: 0
机构:
Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USAUniv N Carolina, Lineberger Comprehens Canc Ctr, Dept Biochem & Biophys, Howard Hughes Med Inst, Chapel Hill, NC 27599 USA
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Ling, JQ
Li, T
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Li, T
Hu, JF
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Hu, JF
Vu, TH
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Vu, TH
Chen, HL
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Chen, HL
Qiu, XW
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Qiu, XW
Cherry, AM
论文数: 0引用数: 0
h-index: 0
机构:Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
Cherry, AM
Hoffman, AR
论文数: 0引用数: 0
h-index: 0
机构:
Palo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USAPalo Alto Hlth Care Syst, Dept Vet Affairs, Med Serv, Palo Alto, CA 94304 USA
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Ng, MHL
Chung, YF
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Chung, YF
Lo, KW
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Lo, KW
Wickham, NWR
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Wickham, NWR
Lee, JCK
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG
Lee, JCK
Huang, DP
论文数: 0引用数: 0
h-index: 0
机构:
CHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONGCHINESE UNIV HONG KONG,PRINCE WALES HOSP,DEPT CLIN ONCOL,SHATIN,NT,HONG KONG