Epigenetics of human T cells during the G₀→G₁ transition

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.

Asymmetric cancer cell division regulated by AKT

“…1 C-E and Fig. S1A) (2,(9)(10)(11)(12). Notably, ROS low cells were not unique to MCF7; we could also find similar slowly cycling cells in the MDA-MB-231 breast and HCT116 colon cancer lines (Fig.…”

Epigenetic Control of Inducible Gene Expression in the Immune System

“…It could be that many inducible genes, as those discussed in the section earlier, already display a sufficiently active chromatin configuration that does not require further alteration for increased gene www.futuremedicine.com activity. These studies on human CD4 + T cells suggests that many genes are primed for activation prior to gene induction, and TCR stimulation would recruit transcription factors that direct the necessary chromatin changes for transcription to occur [19,20,89]. This is supported by studies on individual genes, which discovered instances where inducible genes had promoters that in certain aspects resembled those of active genes.…”

“…While there is evidence of inducible genes showing changes in chromatin structure upon activation, interestingly some studies on rapidly inducible genes associated with active marks such as histone acetylation and H3K4me3 show no significant change in these marks following T-cell activation [19,20,56,57,89]. It could be that many inducible genes, as those discussed in the section earlier, already display a sufficiently active chromatin configuration that does not require further alteration for increased gene www.futuremedicine.com activity.…”

“…In immune cells, some activated lymphocytes will differentiate into memory lymphocytes and these cells induce many genes more quickly (or to a greater level) than naive cells, allowing the body to respond more quickly to an infection. Indeed, genome-wide studies have made observations that the T-cell population studied was most likely to have both naive and memory T cells [57,89]. These studies postulated that the pool of memory T cells would have been exposed to an antigen and retain the chromatin state of previous inductions but remains dormant until future antigenic encounters [57,89].…”

“…Indeed, genome-wide studies have made observations that the T-cell population studied was most likely to have both naive and memory T cells [57,89]. These studies postulated that the pool of memory T cells would have been exposed to an antigen and retain the chromatin state of previous inductions but remains dormant until future antigenic encounters [57,89]. Several groups have proposed that this 'memory' of previous activation is encoded by the chromatin at the promoters of the more easily activated genes [108][109][110].…”