Structure and mechanism of the RNA polymerase II transcription machinery

Genes & Development, Journal Year: 2020, Volume and Issue: 34(7-8), P. 465 - 488

Published: April 1, 2020

RNA polymerase II (Pol II) transcribes all protein-coding genes and many noncoding RNAs in eukaryotic genomes. Although Pol is a complex, 12-subunit enzyme, it lacks the ability to initiate transcription cannot consistently transcribe through long DNA sequences. To execute these essential functions, an array of proteins protein complexes interact with regulate its activity. In this review, we detail structure mechanism over dozen factors that govern initiation (e.g., TFIID, TFIIH, Mediator), pausing, elongation DSIF, NELF, PAF, P-TEFb). The structural basis for regulation has advanced rapidly past decade, largely due technological innovations cryoelectron microscopy. Here, summarize wealth functional data have enabled deeper understanding mechanisms; also highlight mechanistic questions remain unanswered or controversial.

Language: Английский

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Epigenetic regulation of the histone-to-protamine transition during spermiogenesis

Reproduction, Journal Year: 2016, Volume and Issue: 151(5), P. R55 - R70

Published: April 29, 2016

Abstract In mammals, male germ cells differentiate from haploid round spermatids to flagella-containing motile sperm in a process called spermiogenesis. This is distinct somatic cell differentiation that the majority of core histones are replaced sequentially, first by transition proteins and then protamines, facilitating chromatin hyper-compaction. histone-to-protamine represents an excellent model for investigation how epigenetic regulators interact with each other remodel architecture. Although early work field highlighted critical roles testis-specific transcription factors controlling haploid-specific developmental program, recent studies underscore essential functions players involved dramatic genome remodeling takes place during wholesale histone replacement. this review, we discuss advances our understanding players, such as variants writers/readers/erasers, rewire spermatid facilitate substitution protamines mammals.

Language: Английский

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Nascent RNA analyses: tracking transcription and its regulation

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(12), P. 705 - 723

Published: Aug. 9, 2019

Language: Английский

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Epigenetics and Trained Immunity

Antioxidants and Redox Signaling, Journal Year: 2017, Volume and Issue: 29(11), P. 1023 - 1040

Published: Oct. 5, 2017

A growing body of clinical and experimental evidence has challenged the traditional understanding that only adaptive immune system can mount immunological memory. Recent findings describe characteristics innate system, underscored by its ability to remember antecedent foreign encounters respond in a nonspecific sensitized manner reinfection. This been termed trained immunity. Although beneficial context recurrent infections, this might actually contribute chronic immune-mediated diseases, such as atherosclerosis. Advances: In line with proposed role sustaining cellular memories, epigenetic reprogramming emerged critical determinant technological computational advances improve unbiased acquisition epigenomic profiles have significantly enhanced our appreciation for complexities chromatin architecture contexts diverse challenges.Key resolving distinct signatures memory is comprehensive precise physiological targets regulatory proteins recognize, deposit, remove chemical modifications from well other gene-regulating factors. Drawing rapidly expanding compendium studies, review details current perspective pathways support adapted phenotypes monocytes macrophages.We explore future strategies are aimed at exploiting mechanism immunity prevention treatment infections disorders.

Language: Английский

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SMN and symmetric arginine dimethylation of RNA polymerase II C-terminal domain control termination

Nature, Journal Year: 2015, Volume and Issue: 529(7584), P. 48 - 53

Published: Dec. 23, 2015

Language: Английский

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