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Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology

The CCCTC-binding factor CTCF is the only known vertebrate insulator protein and has been shown to regulate important developmental processes such as imprinting, X-chromosome inactivation and genomic architecture. In this study, we examined the role of CTCF in human embryonic stem cell (hESC) biolog...

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Autores principales: Balakrishnan, Sri Kripa, Witcher, Michael, Berggren, Travis W., Emerson, Beverly M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411781/
https://www.ncbi.nlm.nih.gov/pubmed/22879976
http://dx.doi.org/10.1371/journal.pone.0042424
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author Balakrishnan, Sri Kripa
Witcher, Michael
Berggren, Travis W.
Emerson, Beverly M.
author_facet Balakrishnan, Sri Kripa
Witcher, Michael
Berggren, Travis W.
Emerson, Beverly M.
author_sort Balakrishnan, Sri Kripa
collection PubMed
description The CCCTC-binding factor CTCF is the only known vertebrate insulator protein and has been shown to regulate important developmental processes such as imprinting, X-chromosome inactivation and genomic architecture. In this study, we examined the role of CTCF in human embryonic stem cell (hESC) biology. We demonstrate that CTCF associates with several important pluripotency genes, including NANOG, SOX2, cMYC and LIN28 and is critical for hESC proliferation. CTCF depletion impacts expression of pluripotency genes and accelerates loss of pluripotency upon BMP4 induced differentiation, but does not result in spontaneous differentiation. We find that CTCF associates with the distal ends and internal sites of the co-regulated 160 kb NANOG-DPPA3-GDF3 locus. Each of these sites can function as a CTCF-dependent enhancer-blocking insulator in heterologous assays. In hESCs, CTCF exists in multisubunit protein complexes and can be poly(ADP)ribosylated. Known CTCF cofactors, such as Cohesin, differentially co-localize in the vicinity of specific CTCF binding sites within the NANOG locus. Importantly, the association of some cofactors and protein PARlation selectively changes upon differentiation although CTCF binding remains constant. Understanding how unique cofactors may impart specialized functions to CTCF at specific genomic locations will further illuminate its role in stem cell biology.
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spelling pubmed-34117812012-08-09 Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology Balakrishnan, Sri Kripa Witcher, Michael Berggren, Travis W. Emerson, Beverly M. PLoS One Research Article The CCCTC-binding factor CTCF is the only known vertebrate insulator protein and has been shown to regulate important developmental processes such as imprinting, X-chromosome inactivation and genomic architecture. In this study, we examined the role of CTCF in human embryonic stem cell (hESC) biology. We demonstrate that CTCF associates with several important pluripotency genes, including NANOG, SOX2, cMYC and LIN28 and is critical for hESC proliferation. CTCF depletion impacts expression of pluripotency genes and accelerates loss of pluripotency upon BMP4 induced differentiation, but does not result in spontaneous differentiation. We find that CTCF associates with the distal ends and internal sites of the co-regulated 160 kb NANOG-DPPA3-GDF3 locus. Each of these sites can function as a CTCF-dependent enhancer-blocking insulator in heterologous assays. In hESCs, CTCF exists in multisubunit protein complexes and can be poly(ADP)ribosylated. Known CTCF cofactors, such as Cohesin, differentially co-localize in the vicinity of specific CTCF binding sites within the NANOG locus. Importantly, the association of some cofactors and protein PARlation selectively changes upon differentiation although CTCF binding remains constant. Understanding how unique cofactors may impart specialized functions to CTCF at specific genomic locations will further illuminate its role in stem cell biology. Public Library of Science 2012-08-03 /pmc/articles/PMC3411781/ /pubmed/22879976 http://dx.doi.org/10.1371/journal.pone.0042424 Text en © 2012 Balakrishnan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Balakrishnan, Sri Kripa
Witcher, Michael
Berggren, Travis W.
Emerson, Beverly M.
Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology
title Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology
title_full Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology
title_fullStr Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology
title_full_unstemmed Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology
title_short Functional and Molecular Characterization of the Role of CTCF in Human Embryonic Stem Cell Biology
title_sort functional and molecular characterization of the role of ctcf in human embryonic stem cell biology
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411781/
https://www.ncbi.nlm.nih.gov/pubmed/22879976
http://dx.doi.org/10.1371/journal.pone.0042424
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