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A CTCF-dependent silencer located in the differentially methylated area may regulate expression of a housekeeping gene overlapping a tissue-specific gene domain 下载免费PDF全文
Klochkov D Rincón-Arano H Ioudinkova ES Valadez-Graham V Gavrilov A Recillas-Targa F Razin SV 《Molecular and cellular biology》2006,26(5):1589-1597
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Chernukhin IV Shamsuddin S Robinson AF Carne AF Paul A El-Kady AI Lobanenkov VV Klenova EM 《The Journal of biological chemistry》2000,275(38):29915-29921
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K. E. Orishchenko E. A. Elisaphenko A. E. Kel S. M. Zakian 《Russian Journal of Genetics》2009,45(10):1182-1191
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Zhang H Niu B Hu JF Ge S Wang H Li T Ling J Steelman BN Qian G Hoffman AR 《The Journal of cell biology》2011,193(3):475-487
Monoallelic expression of IGF2 is regulated by CCCTC binding factor (CTCF) binding to the imprinting control region (ICR) on the maternal allele, with subsequent formation of an intrachromosomal loop to the promoter region. The N-terminal domain of CTCF interacts with SUZ12, part of the polycomb repressive complex-2 (PRC2), to silence the maternal allele. We synthesized decoy CTCF proteins, fusing the CTCF deoxyribonucleic acid-binding zinc finger domain to CpG methyltransferase Sss1 or to enhanced green fluorescent protein. In normal human fibroblasts and breast cancer MCF7 cell lines, the CTCF decoy proteins bound to the unmethylated ICR and to the IGF2 promoter region but did not interact with SUZ12. EZH2, another part of PRC2, was unable to methylate histone H3-K27 in the IGF2 promoter region, resulting in reactivation of the imprinted allele. The intrachromosomal loop between the maternal ICR and the IGF2 promoters was not observed when IGF2 imprinting was lost. CTCF epigenetically governs allelic gene expression of IGF2 by orchestrating chromatin loop structures involving PRC2. 相似文献