Chromatin structure and gene regulation in T cell development and function

Abstract

Transcription factors control gene expression programs in the context of the chromatin structure of their target genes. DNA methylation, post-translational histone modifications such as acetylation and methylation, and higher order chromatin organization allow the maintenance of gene expression patterns through mitosis, but how do they accommodate developmentally regulated changes in gene expression programs? Although histone acetylation and deacetylation are in dynamic equilibrium and mechanisms for the removal of methyl groups from histones are emerging, the extent to which there is active demethylation of DNA remains controversial. Looking at chromatin in the three-dimensional space of the nucleus, recent work demonstrates that gene regulation involves contacts between regulatory elements within genes or gene clusters on the same chromosome (in cis) and between different chromosomes (in trans). Finally, non-coding RNAs make a significant contribution to transcriptional and post-transcriptional gene silencing. Together, these advances contribute to an understanding of how gene expression programs are established, maintained and modified during development.

Adoptive transfer of effector CD8+ T cells derived from central memory cells establishes persistent T cell memory in primates

“…IL-15, which can directly bind to IL-15Rα on T cells or be transpresented by IL-15Rα-bearing cells (38), may be the initial stimulus that enables survival of T CM -derived cells in vivo, although the later acquisition of IL-7Rα on transferred T cells is consistent with a role for IL-7 in the reversion of T E to long-lived T CM (39). Gene expression and epigenetic profiling may provide further insight into the basis for the marked differences in the survival of T E clones derived from T CM and T EM and the ability of T CM -derived clones to reacquire phenotypic and functional properties of T CM (40,41).…”

The early expressed HIV-1 genes regulate DNMT1 expression

“…Clear examples of such processes involving DNA methylation during normal mammalian development include the cell type-specific expression of the maspin gene (SERPIN5) in normal human epithelial cells, and regulation of interleukin 4 (IL4) and IFNγ expression in T cells which influences the T cell differentiation process. 6,[42][43][44] The observation that mammalian viruses can both cause such epigenetic changes within the host genome, and themselves are epigenetically altered, provides opportunities to study their pathogenesis, and the processes leading to epigenetic transcriptional regulation.…”

“…9 The three catalytic mammalian DNA methyltransferases DNMT1, DNMT3α and DNMT3β have varying levels of de novo and maintenance methylation activities. 1,2,6 Although frequently referred to as the "maintenance" enzyme because of its preference for hemimethylated sites, we and others have shown DNMT1 to have significant de novo activity (methylation of unmethylated sites). [13][14][15][16] Interestingly, changes in cellular DNMT1 levels of up to 50-fold result in the aberrant de novo methylation of only a small subset of genes.…”

“…[1][2][3] The major eukaryotic epigenetic mechanisms include DNA methylation, histone modifications and non-coding RNA-mediated transcriptional and post-transcriptional regulation. [4][5][6] DNA methylation is essential for normal mammalian development, and diverse human diseases result from inherited disruptions of the DNA methyltransferase enzymes, or other components of DNA methylation. [7][8][9][10] The post-transcriptional addition of methyl groups to the 5-position of cytosines within the CpG dinucleotide alters the appearance of the major groove of DNA, leading to an alteration of the protein/DNA interface for regulatory DNA binding proteins.…”

Transcribed Guanine-rich RNA Aggregates on Template DNA and Changes Its Conformation

“…4 For example, cytokine gene and ¢-globin gene loci change their conformation in line with cell differentiation. 4,5 The precise mechanism of chromosomal conformation change, however, has not been fully elucidated. In this study, we showed that RNA is essential for determining DNA conformation.…”