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Epigenetic marking prepares the human HOXA cluster for activation during differentiation of pluripotent cells

Lookup NU author(s): Stuart Atkinson, Dr Rebecca Stewart, Professor Majlinda LakoORCiD, Professor Lyle Armstrong

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Abstract

Activation of Hox gene clusters is an early event in embryonic development since individual members play important roles in patterning of the body axis. Their functions require precise control of spatiotemporal expression to provide positional information for the cells of the developing embryo, and the manner by which this control is achieved has generated considerable interest. The situation is different in pluripotent cells, where HOX genes are not expressed but are held in potentio as bivalent chromatin domains, which are resolved upon differentiation to permit HOX cluster activation. In this study we have used differentiation of the pluripotent embryonal carcinoma cell line NTera2SP12 and the human embryonic stem cell line H9 to examine epigenetic changes that accompany activation of the HOXA cluster and show that specific genomic loci are marked by lysine methylation of histone H3 (H3K4 tri- and dimethyl, H3K9 trimethyl) and acetylation of histone H4 even in the undifferentiated cells. The precise locations of such modified histories may be involved in controlling the colinear expression of genes from the cluster.


Publication metadata

Author(s): Atkinson SP, Koch CM, Clelland GK, Willcox S, Fowler JC, Stewart R, Lako M, Dunham I, Armstrong L

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2008

Volume: 26

Issue: 5

Pages: 1174-1185

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: AlphaMed Press

URL: http://dx.doi.org/10.1634/stemcells.2007-0497

DOI: 10.1634/stemcells.2007-0497


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Funding

Funder referenceFunder name
BB/E012841/1Biotechnology and Biological Sciences Research Council
G0301182Medical Research Council

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