Coupling polymerase pausing and chromatin landscapes for precise regulation of transcription
ABSTRACT Altering gene expression in response to stimuli is a pivotal mechanism through which organisms execute developmental programs and respond to changes in their environment. Packaging of promoter DNA into chromatin can greatly impact the ability of RNA polymerase II to access and transcribe a gene. Promoter chromatin environments thus play a central role in establishing transcriptional output appropriate for specific environmental conditions or developmental states. Recent genomic studies have illuminated general principles of chromatin organization and deepened our understanding of how promoter sequence and nucleosome architecture may impact gene expression. Concurrently, pausing of polymerase during early elongation has been recognized as an important event influencing transcription of genes within stimulus-responsive networks. Promoters regulated by pausing are now recognized to possess a distinct chromatin architecture that may facilitate the plasticity of gene expression in response to signaling events. Here we review advances in understanding chromatin and pausing, and explore how coupling Pol II pausing to distinct promoter architectures may help organisms achieve flexible yet precise transcriptional control. This article is part of a Special Issue entitled: Chromatin in time and space.
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ABSTRACT: The inhibitor of differentiation Id2, a protein lacking the basic DNA-binding domain, is involved in the modulation of a number of biological processes. The molecular mechanisms explaining Id2 pleiotropic functions are poorly understood. Id2 and E2F4 are known to bind simultaneously to c-myc promoter. To study whether Id2 plays a global role on transcriptional regulation, we performed in vivo genome-wide ChIP/chip experiments for Id2 and E2F4 in adult mouse liver. An Id2-containing complex was bound to a common sequence downstream from the TSS on a subset of 442 E2F4 target genes mainly related to cell development and chromatin structure. We found a positive correlation between Id2 protein levels and the expression of E2F4/Id2 targets in fetal and adult liver. Id2 protein stability increased in fetal liver by interaction with USP1 de-ubiquitinating enzyme, which was induced during development. In adult liver, USP1 and Id2 levels dramatically decreased. In differentiated liver tissue, when Id2 concentration was low, E2F4/Id2 was bound to the same region as paused Pol II and target genes remained transcriptionally inactive. Conversely, in fetal liver when Id2 levels were increased, Id2 and Pol II were released from gene promoters and target genes up-regulated. During liver regeneration after partial hepatectomy, we obtained the same results as in fetal liver. Our results suggest that Id2 might be part of a reversible development-related program involved in the paused-ON/OFF state of Pol II on selected genes that would remain responsive to specific stimuli.Cellular and Molecular Life Sciences CMLS 02/2014; DOI:10.1007/s00018-014-1588-1 · 5.86 Impact Factor
Article: Epigenetic Control of Immunity[Show abstract] [Hide abstract]
ABSTRACT: Immunity relies on the heterogeneity of immune cells and their ability to respond to pathogen challenges. In the adaptive immune system, lymphocytes display a highly diverse antigen receptor repertoire that matches the vast diversity of pathogens. In the innate immune system, the cell's heterogeneity and phenotypic plasticity enable flexible responses to changes in tissue homeostasis caused by infection or damage. The immune responses are calibrated by the graded activity of immune cells that can vary from yeast-like proliferation to lifetime dormancy. This article describes key epigenetic processes that contribute to the function of immune cells during health and disease.Cold Spring Harbor perspectives in biology 07/2014; 6(6). DOI:10.1101/cshperspect.a019307 · 8.23 Impact Factor
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ABSTRACT: One of the key events in eukaryotic gene regulation and consequent transcription is the assembly of general transcription factors and RNA polymerase II into a functional pre-initiation complex at core promoters. An emerging view of complexity arising from a variety of promoter associated DNA motifs, their binding factors and recent discoveries in characterising promoter associated chromatin properties brings an old question back into the limelight: how is a promoter defined? In addition to position-dependent DNA sequence motifs, accumulating evidence suggests that several parallel acting mechanisms are involved in orchestrating a pattern marked by the state of chromatin and general transcription factor binding in preparation for defining transcription start sites. In this review we attempt to summarise these promoter features and discuss the available evidence pointing at their interactions in defining transcription initiation in developmental contexts. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development, edited by Dr. Peter Verrijzer and Dr. Elissa Lei.Biochimica et Biophysica Acta 11/2013; DOI:10.1016/j.bbagrm.2013.11.003 · 4.66 Impact Factor