The essential and multifunctional TFIIH complex

Protein Science, Год журнала: 2018, Номер 27(6), С. 1018 - 1037

Опубликована: Апрель 17, 2018

Abstract TFIIH is a 10‐subunit complex that regulates RNA polymerase II (pol II) transcription but also serves other important biological roles. Although much remains unknown about function in eukaryotic cells, progress has been made even just the past few years, due part to technological advances (e.g. cryoEM and single molecule methods) development of chemical inhibitors enzymes. This review focuses on major cellular roles for TFIIH, with an emphasis as regulator pol transcription. We describe structure its initiation, promoter‐proximal pausing, elongation, termination. discuss beyond DNA repair, cell cycle regulation) summarize small diseases associated defects function.

Язык: Английский

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Dynamic Competition of Polycomb and Trithorax in Transcriptional Programming

Annual Review of Biochemistry, Год журнала: 2020, Номер 89(1), С. 235 - 253

Опубликована: Янв. 13, 2020

Predicting regulatory potential from primary DNA sequences or transcription factor binding patterns is not possible. However, the annotation of genome by chromatin proteins, histone modifications, and differential compaction largely sufficient to reveal locations genes their activity states. The Polycomb Group (PcG) Trithorax (TrxG) proteins are central players in this cell type-specific organization. PcG function was originally viewed as being solely repressive irreversible, observed at homeotic loci flies mammals. it now clear that modular reversible essential most developmental genes. Focusing mainly on recent advances, we review evidence for how TrxG change dynamically during type transitions. ability implement transcriptional programming with exquisite fidelity normal development.

Язык: Английский

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Epigenetic regulation in development: is the mouse a good model for the human?

Human Reproduction Update, Год журнала: 2018, Номер 24(5), С. 556 - 576

Опубликована: Июнь 5, 2018

Over the past few years, advances in molecular technologies have allowed unprecedented mapping of epigenetic modifications gametes and during early embryonic development. This work is allowing a detailed genomic analysis, which for first time can answer long-standing questions about regulation reprogramming, highlights differences between mouse human, implications are only beginning to be explored. In this review, we summarise new low-cell methods enabling interrogation information embryos, mechanistic insights these provided, contrast findings human. Relevant studies were identified by PubMed search. We discuss levels regulation, from DNA chromatin organisation, gametogenesis, fertilisation pre- post-implantation The recently characterised features oocyte epigenome highlight its exceptionally unique regulatory landscape. organisation landscape both gametic genomes rapidly reprogrammed after fertilisation. extensive remodelling necessary zygotic genome activation, but link remains unclear. While vast majority erased pre-implantation development, suggest that repressive histone may mediate novel mechanism imprinting. To date, characterisation epigenetics human development has been almost exclusively limited methylation profiling; data reinforce global dynamics conserved However, as look closer, it becoming apparent mechanisms regulating distinct. These emphasise importance investigations fundamental humans. Failures implicated disease infertility. With increasing maternal age use reproductive countries all over world, ever more important understand processes required establish developmentally competent embryo. Furthermore, essential evaluate extent patterns sensitive such other adverse environmental exposures.

Язык: Английский

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Diet and the epigenome

Nature Communications, Год журнала: 2018, Номер 9(1)

Опубликована: Авг. 17, 2018

Over the past decade, remarkable breakthroughs in our understanding of epigenetic biology have coincided with an increased public interest impact diet and lifestyle choices on health. It is well established that a balanced enhances life expectancy helps to prevent or treat certain diseases, such as obesity, diabetes, cancer, mental disorders. However, biological mechanisms underlying these effects are not yet understood. In this commentary, we highlight several recent studies report potential link between dietary factors alterations pathways, providing compelling insight into possible environmental fundamental processes.

Язык: Английский

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Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance

Nucleic Acids Research, Год журнала: 2020, Номер 48(20), С. 11380 - 11393

Опубликована: Окт. 16, 2020

Advancing the molecular knowledge surrounding fertility and inheritance has become critical given halving of sperm counts in last 40 years, rise complex disease which cannot be explained by genetics alone. The connection between both these trends may lie alterations to epigenome occur through environmental exposures. Changes are also associated with health risks across generations such as metabolic disorders cancer. Thus, it is imperative identify epigenetic modifications that escape reprogramming during spermatogenesis embryogenesis. Here, we aimed chromatin signature(s) involved transgenerational phenotypes our genetic mouse model overexpresses histone demethylase KDM1A their germ cells. We used sperm-specific immunoprecipitation followed depth sequencing (ChIP-seq), computational analysis whether differential enrichment H3 lysine 4 trimethylation (H3K4me3), 27 (H3K27me3) serve mechanisms for paternal germline. Our on transgenic males revealed specific changes H3K4me3 predominantly occurred independently from bivalent H3K4me3/H3K27me3 regions. Many regions altered were identified allele pre-implantation embryo. These findings suggest functions transmission non-genetic transgenerationally.

Язык: Английский

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