Epigenetics of human T cells during the G0→G1 transition

Alexander E. Smith; Constantinos Chronis; Manolis Christodoulakis; Stephen J. Orr; Nicholas C. Lea; Natalie A. Twine; Akshay Bhinge; Ghulam J. Mufti; N. Shaun B. Thomas

doi:10.1101/gr.085530.108

Epigenetics of human T cells during the G₀→G₁ transition

¹ King's College London, Department of Haematological Medicine, Leukaemia Sciences Laboratories, Rayne Institute, London SE5 9NU, United Kingdom;
² King's College London, Department of Computer Science, London WC2R 2LS, United Kingdom;
³ University of Texas at Austin, Department of Chemistry and Biochemistry, Institute for Cellular and Molecular Biology, Austin, Texas 78712-0159, USA

↵4 These authors contributed equally to this work and are joint first authors.

Abstract

We investigated functional epigenetic changes that occur in primary human T lymphocytes during entry into the cell cycle and mapped these at the single-nucleosome level by ChIP-chip on tiling arrays for chromosomes 1 and 6. We show that nucleosome loss and flanking active histone marks define active transcriptional start sites (TSSs). Moreover, these signatures are already set at many inducible genes in quiescent cells prior to cell stimulation. In contrast, there is a dearth of the inactive histone mark H3K9me3 at the TSS, and under-representation of H3K9me2 and H3K9me3 defines the body of active genes. At the DNA level, cytosine methylation (meC) is enriched for nucleosomes that remain at the TSS, whereas in general there is a dearth of meC at TSSs. Furthermore, a drop in meC also marks 3′ transcription termination, and a peak of meC occurs at stop codons. This mimics the 3′ nucleosomal distribution in yeast, which we show does not occur in human T cells.

Footnotes

↵5 Present address: School of Computing & Technology, University of East London, Docklands Campus, 4-6 University Way, London E16 2RD, UK.
↵6 Corresponding author.

E-mail nicholas.s.thomas{at}kcl.ac.uk; fax 44-(0)-20-7733-3877.
[Supplemental material is available online at www.genome.org. The array data from this study have been submitted to ArrayExpress (http://www.ebi.ac.uk/microarray-as/ae/) under accession no. E-MEXP-2188.]
Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.085530.108.
- Received August 28, 2008.
- Accepted May 13, 2009.