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Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II

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 rep...

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Autores principales: Zhang, He, Niu, Beibei, Hu, Ji-Fan, Ge, Shengfang, Wang, Haibo, Li, Tao, Ling, Jianqun, Steelman, Brandon N., Qian, Guanxiang, Hoffman, Andrew R.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087012/
https://www.ncbi.nlm.nih.gov/pubmed/21536749
http://dx.doi.org/10.1083/jcb.201101021
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author Zhang, He
Niu, Beibei
Hu, Ji-Fan
Ge, Shengfang
Wang, Haibo
Li, Tao
Ling, Jianqun
Steelman, Brandon N.
Qian, Guanxiang
Hoffman, Andrew R.
author_facet Zhang, He
Niu, Beibei
Hu, Ji-Fan
Ge, Shengfang
Wang, Haibo
Li, Tao
Ling, Jianqun
Steelman, Brandon N.
Qian, Guanxiang
Hoffman, Andrew R.
author_sort Zhang, He
collection PubMed
description 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.
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spelling pubmed-30870122011-11-02 Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II Zhang, He Niu, Beibei Hu, Ji-Fan Ge, Shengfang Wang, Haibo Li, Tao Ling, Jianqun Steelman, Brandon N. Qian, Guanxiang Hoffman, Andrew R. J Cell Biol Research Articles 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. The Rockefeller University Press 2011-05-02 /pmc/articles/PMC3087012/ /pubmed/21536749 http://dx.doi.org/10.1083/jcb.201101021 Text en © 2011 Zhang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Zhang, He
Niu, Beibei
Hu, Ji-Fan
Ge, Shengfang
Wang, Haibo
Li, Tao
Ling, Jianqun
Steelman, Brandon N.
Qian, Guanxiang
Hoffman, Andrew R.
Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II
title Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II
title_full Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II
title_fullStr Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II
title_full_unstemmed Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II
title_short Interruption of intrachromosomal looping by CCCTC binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor II
title_sort interruption of intrachromosomal looping by ccctc binding factor decoy proteins abrogates genomic imprinting of human insulin-like growth factor ii
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3087012/
https://www.ncbi.nlm.nih.gov/pubmed/21536749
http://dx.doi.org/10.1083/jcb.201101021
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