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

¹ North East Institute for Stem Cell Research and Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, NE1 3BZ, UK
² The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

^* To whom correspondence should be addressed. E-mail: Lyle.Armstrong{at}ncl.ac.uk.

	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 spatio-temporal 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 di-methyl, 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 co-linear expression of genes from the cluster.