Hox in motion: tracking HoxA cluster conformation during differentiation

Three-dimensional genome organization is an important higher order transcription regulation mechanism that can be studied with the chromosome conformation capture techniques. Here, we combined chromatin organization analysis by chromosome conformation capture-carbon copy, computational modeling and...

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Main Authors:	Rousseau, Mathieu, Crutchley, Jennifer L., Miura, Hisashi, Suderman, Matthew, Blanchette, Mathieu, Dostie, Josée
Format:	Online
Language:	English
Published:	Oxford University Press 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919592/

id	pubmed-3919592
recordtype	oai_dc
spelling	pubmed-39195922014-02-10 Hox in motion: tracking HoxA cluster conformation during differentiation Rousseau, Mathieu Crutchley, Jennifer L. Miura, Hisashi Suderman, Matthew Blanchette, Mathieu Dostie, Josée Gene Regulation, Chromatin and Epigenetics Three-dimensional genome organization is an important higher order transcription regulation mechanism that can be studied with the chromosome conformation capture techniques. Here, we combined chromatin organization analysis by chromosome conformation capture-carbon copy, computational modeling and epigenomics to achieve the first integrated view, through time, of a connection between chromatin state and its architecture. We used this approach to examine the chromatin dynamics of the HoxA cluster in a human myeloid leukemia cell line at various stages of differentiation. We found that cellular differentiation involves a transient activation of the 5′-end HoxA genes coinciding with a loss of contacts throughout the cluster, and by specific silencing at the 3′-end with H3K27 methylation. The 3D modeling of the data revealed an extensive reorganization of the cluster between the two previously reported topologically associated domains in differentiated cells. Our results support a model whereby silencing by polycomb group proteins and reconfiguration of CTCF interactions at a topologically associated domain boundary participate in changing the HoxA cluster topology, which compartmentalizes the genes following differentiation. Oxford University Press 2014-02 2013-10-29 /pmc/articles/PMC3919592/ /pubmed/24174538 http://dx.doi.org/10.1093/nar/gkt998 Text en © The Author(s) 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rousseau, Mathieu Crutchley, Jennifer L. Miura, Hisashi Suderman, Matthew Blanchette, Mathieu Dostie, Josée
spellingShingle	Rousseau, Mathieu Crutchley, Jennifer L. Miura, Hisashi Suderman, Matthew Blanchette, Mathieu Dostie, Josée Hox in motion: tracking HoxA cluster conformation during differentiation
author_facet	Rousseau, Mathieu Crutchley, Jennifer L. Miura, Hisashi Suderman, Matthew Blanchette, Mathieu Dostie, Josée
author_sort	Rousseau, Mathieu
title	Hox in motion: tracking HoxA cluster conformation during differentiation
title_short	Hox in motion: tracking HoxA cluster conformation during differentiation
title_full	Hox in motion: tracking HoxA cluster conformation during differentiation
title_fullStr	Hox in motion: tracking HoxA cluster conformation during differentiation
title_full_unstemmed	Hox in motion: tracking HoxA cluster conformation during differentiation
title_sort	hox in motion: tracking hoxa cluster conformation during differentiation
description	Three-dimensional genome organization is an important higher order transcription regulation mechanism that can be studied with the chromosome conformation capture techniques. Here, we combined chromatin organization analysis by chromosome conformation capture-carbon copy, computational modeling and epigenomics to achieve the first integrated view, through time, of a connection between chromatin state and its architecture. We used this approach to examine the chromatin dynamics of the HoxA cluster in a human myeloid leukemia cell line at various stages of differentiation. We found that cellular differentiation involves a transient activation of the 5′-end HoxA genes coinciding with a loss of contacts throughout the cluster, and by specific silencing at the 3′-end with H3K27 methylation. The 3D modeling of the data revealed an extensive reorganization of the cluster between the two previously reported topologically associated domains in differentiated cells. Our results support a model whereby silencing by polycomb group proteins and reconfiguration of CTCF interactions at a topologically associated domain boundary participate in changing the HoxA cluster topology, which compartmentalizes the genes following differentiation.
publisher	Oxford University Press
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919592/
_version_	1612056777863462912

Hox in motion: tracking HoxA cluster conformation during differentiation

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