Polycomb group proteins maintain the gene-expression pattern of different cells that is set during early development by regulating chromatin structure. In mammals, two main Polycomb group complexes ...exist - Polycomb repressive complex 1 (PRC1) and 2 (PRC2). PRC1 compacts chromatin and catalyses the monoubiquitylation of histone H2A. PRC2 also contributes to chromatin compaction, and catalyses the methylation of histone H3 at lysine 27. PRC2 is involved in various biological processes, including differentiation, maintaining cell identity and proliferation, and stem-cell plasticity. Recent studies of PRC2 have expanded our perspectives on its function and regulation, and uncovered a role for non-coding RNA in the recruitment of PRC2 to target genes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chromatin domains rich in inheritance Reinberg, Danny; Vales, Lynne D
Science (American Association for the Advancement of Science),
07/2018, Letnik:
361, Številka:
6397
Journal Article
Recenzirano
Only certain histone posttranslational modifications qualify as being epigenetic
Epigenetic phenomena are heritable changes to gene expression that occur without changes to the DNA sequence and that ...include posttranslational modifications (PTMs) to the histones that package DNA into chromatin. These PTMs are deposited on histones by enzymes in response to an “initiator,” ultimately altering chromatin structure and, accordingly, gene expression. In multicellular organisms, cellular identity is established by master regulators (initiators) that can activate or repress transcription through their sequence-specific DNA binding activity. The accurate transmission of distinct gene expression profiles during cell division is essential for preserving the properties of cell lineages. Thus, a key feature of the epigenetic process is that after the initiator subsides, these informative chromatin PTMs must be inherited by subsequent cell generations. Numerous histone PTMs can occur, but can they all convey epigenetic information? We discuss the few histone PTMs that qualify as epigenetic and the distinct features of the enzymes that deposit them that account for their epigenetic status.
Although it is widely accepted that the regulation of the chromatin landscape is pivotal to conveying the epigenetic program, it is still unclear how a defined chromatin domain is reproduced ...following DNA replication and transmitted from one cell generation to the next. Here, we review the multiple mechanisms that potentially affect the inheritance of epigenetic information in somatic cells. We consider models of how histones might be recycled following replication, and discuss the importance of positive-feedback loops, long-range gene interactions and the complex network of trans-acting factors in the transmission of chromatin states.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
In this review, Prendergast and Reinberg discuss the likelihood that the family of histone H1 variants may be key to understanding several fundamental processes in chromatin biology and underscore ...their particular contributions to distinctly significant chromatin-related processes.
Major advances in the chromatin and epigenetics fields have uncovered the importance of core histones, histone variants and their post-translational modifications (PTMs) in modulating chromatin structure. However, an acutely understudied related feature of chromatin structure is the role of linker histone H1. Previous assumptions of the functional redundancy of the 11 nonallelic H1 variants are contrasted by their strong evolutionary conservation, variability in their potential PTMs, and increased reports of their disparate functions, sub-nuclear localizations and unique expression patterns in different cell types. The commonly accepted notion that histone H1 functions solely in chromatin compaction and transcription repression is now being challenged by work from multiple groups. These studies highlight histone H1 variants as underappreciated facets of chromatin dynamics that function independently in various chromatin-based processes. In this review, we present notable findings involving the individual somatic H1 variants of which there are seven, underscoring their particular contributions to distinctly significant chromatin-related processes.
Molecular Signals of Epigenetic States Bonasio, Roberto; Tu, Shengjiang; Reinberg, Danny
Science (American Association for the Advancement of Science),
10/2010, Letnik:
330, Številka:
6004
Journal Article
Recenzirano
Odprti dostop
Epigenetic signals are responsible for the establishment, maintenance, and reversal of metastable transcriptional states that are fundamental for the cell's ability to "remember" past events, such as ...changes in the external environment or developmental cues. Complex epigenetic states are orchestrated by several converging and reinforcing signals, including transcription factors, noncoding RNAs, DNA methylation, and histone modifications. Although all of these pathways modulate transcription from chromatin in vivo, the mechanisms by which epigenetic information is transmitted through cell division remain unclear. Because epigenetic states are metastable and change in response to the appropriate signals, a deeper understanding of their molecular framework will allow us to tackle the dysregulation of epigenetics in disease.
A double take on bivalent promoters Voigt, Philipp; Tee, Wee-Wei; Reinberg, Danny
Genes & development,
2013-Jun-15, 2013-06-15, 20130615, Letnik:
27, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Histone modifications and chromatin-associated protein complexes are crucially involved in the control of gene expression, supervising cell fate decisions and differentiation. Many promoters in ...embryonic stem (ES) cells harbor a distinctive histone modification signature that combines the activating histone H3 Lys 4 trimethylation (H3K4me3) mark and the repressive H3K27me3 mark. These bivalent domains are considered to poise expression of developmental genes, allowing timely activation while maintaining repression in the absence of differentiation signals. Recent advances shed light on the establishment and function of bivalent domains; however, their role in development remains controversial, not least because suitable genetic models to probe their function in developing organisms are missing. Here, we explore avenues to and from bivalency and propose that bivalent domains and associated chromatin-modifying complexes safeguard proper and robust differentiation.
Gene expression programmes conferring cellular identity are achieved through the organization of chromatin structures that either facilitate or impede transcription. Among the key determinants of ...chromatin organization are the histone modifications that correlate with a given transcriptional status and chromatin state. Until recently, the details for the segregation of nucleosomes on DNA replication and their implications in re-establishing heritable chromatin domains remained unclear. Here, we review recent findings detailing the local segregation of parental nucleosomes and highlight important advances as to how histone methyltransferases associated with the establishment of repressive chromatin domains facilitate epigenetic inheritance.
Histones: annotating chromatin Campos, Eric I; Reinberg, Danny
Annual review of genetics,
12/2009, Letnik:
43
Journal Article
Recenzirano
Chromatin is a highly regulated nucleoprotein complex through which genetic material is structured and maneuvered to elicit cellular processes, including transcription, cell division, ...differentiation, and DNA repair. In eukaryotes, the core of this structure is composed of nucleosomes, or repetitive histone octamer units typically enfolded by 147 base pairs of DNA. DNA is arranged and indexed through these nucleosomal structures to adjust local chromatin compaction and accessibility. Histones are subject to multiple covalent posttranslational modifications, some of which alter intrinsic chromatin properties, others of which present or hinder binding modules for non-histone, chromatin-modifying complexes. Although certain histone marks correlate with different biological outputs, we have yet to fully appreciate their effects on transcription and other cellular processes. Tremendous advancements over the past years have uncovered intriguing histone-related matters and raised important related questions. This review revisits past breakthroughs and discusses novel developments that pertain to histone posttranslational modifications and the affects they have on transcription and DNA packaging.
As the process that silences gene expression ensues during development, the stage is set for the activity of Polycomb-repressive complex 2 (PRC2) to maintain these repressed gene profiles. PRC2 ...catalyzes a specific histone posttranslational modification (hPTM) that fosters chromatin compaction. PRC2 also facilitates the inheritance of this hPTM through its self-contained "write and read" activities, key to preserving cellular identity during cell division. As these changes in gene expression occur without changes in DNA sequence and are inherited, the process is epigenetic in scope. Mutants of mammalian PRC2 or of its histone substrate contribute to the cancer process and other diseases, and research into these aberrant pathways is yielding viable candidates for therapeutic targeting. The effectiveness of PRC2 hinges on its being recruited to the proper chromatin sites; however, resolving the determinants to this process in the mammalian case was not straightforward and thus piqued the interest of many in the field. Here, we chronicle the latest advances toward exposing mammalian PRC2 and its high maintenance.
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