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First published online February 21, 2008
Stem Cells Vol. 26 No. 5 May 2008, pp. 1174 -1185
doi:10.1634/stemcells.2007-0497; www.StemCells.com
© 2008 AlphaMed Press

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STEM CELL GENOMICS AND PROTEOMICS

Epigenetic Marking Prepares the Human HOXA Cluster for Activation During Differentiation of Pluripotent Cells

Stuart P. Atkinsona,b, Christoph M. Kochc, Gayle K. Clellandc, Sarah Willcoxc, Joanna C. Fowlerc, Rebecca Stewarta,b, Majlinda Lakoa,b, Ian Dunhamc, Lyle Armstronga,b

aNorth East Institute for Stem Cell Research and
bInstitute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Newcastle upon Tyne, United Kingdom;
cThe Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom

Key Words. HOXA genes • Embryonic stem cells • Embryonal carcinoma cells

Correspondence: Lyle Armstrong, B.Sc., Ph.D., International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, United Kingdom. Telephone: 00-44-191-241-8695; Fax: 00-44-191-241-8666; e-mail: Lyle.Armstrong{at}ncl.ac.uk

Received June 25, 2007; accepted for publication February 14, 2008.
First published online in STEM CELLS EXPRESS   February 21, 2008.



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 histones may be involved in controlling the colinear expression of genes from the cluster.

Disclosure of potential conflicts of interest is found at the end of this article.






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