Chromatin replication and epigenetic cell memory

Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(4), P. 361 - 371

Published: March 30, 2020

Language: Английский

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PRC2 is high maintenance

Genes & Development, Journal Year: 2019, Volume and Issue: 33(15-16), P. 903 - 935

Published: May 23, 2019

As the process that silences gene expression ensues during development, stage is set for activity of Polycomb-repressive complex 2 (PRC2) to maintain these repressed profiles. PRC2 catalyzes a specific histone posttranslational modification (hPTM) fosters chromatin compaction. also facilitates inheritance this hPTM through its self-contained “write and read” activities, key preserving cellular identity cell division. changes in occur without DNA sequence are inherited, epigenetic scope. Mutants mammalian or substrate contribute cancer other diseases, research into aberrant pathways yielding viable candidates therapeutic targeting. The effectiveness hinges on being recruited proper sites; however, resolving determinants case was not straightforward thus piqued interest many field. Here, we chronicle latest advances toward exposing high maintenance.

Language: Английский

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A mechanism for preventing asymmetric histone segregation onto replicating DNA strands

Science, Journal Year: 2018, Volume and Issue: 361(6409), P. 1386 - 1389

Published: Aug. 16, 2018

How parental histone (H3-H4)2 tetramers, the primary carriers of epigenetic modifications, are transferred onto leading and lagging strands DNA replication forks for inheritance remains elusive. Here we show that tetramers assembled into nucleosomes both strands, with a slight preference strands. The lagging-strand increases markedly in budding yeast cells lacking Dpb3 Dpb4, two subunits strand polymerase, Pol ε, owing to impairment transfer Dpb3-Dpb4 binds H3-H4 vitro participates heterochromatin. These results indicate different proteins facilitate versus Dbp3-Dpb4 plays an important role this poorly understood process.

Language: Английский

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Accurate Recycling of Parental Histones Reproduces the Histone Modification Landscape during DNA Replication

Molecular Cell, Journal Year: 2018, Volume and Issue: 72(2), P. 239 - 249.e5

Published: Aug. 23, 2018

Language: Английский

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The Complexity of PRC2 Subcomplexes

Trends in Cell Biology, Journal Year: 2019, Volume and Issue: 29(8), P. 660 - 671

Published: June 6, 2019

Polycomb repressive complex 2 (PRC2) is a multisubunit protein essential for the development of multicellular organisms. Recruitment PRC2 to target genes, followed by deposition and propagation its catalytic product histone H3 lysine 27 trimethylation (H3K27me3), are key spatiotemporal control developmental gene expression. Recent breakthrough studies have uncovered unexpected roles substoichiometric subunits in these processes. Here, we elaborate on how facultative regulate activity, locus-specific binding, H3K27me3, this affects chromatin structure, expression, cell fate.

Language: Английский

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Embryonic timing, axial stem cells, chromatin dynamics, and the Hox clock

Genes & Development, Journal Year: 2017, Volume and Issue: 31(14), P. 1406 - 1416

Published: July 15, 2017

Collinear regulation of Hox genes in space and time has been an outstanding question ever since the initial work Ed Lewis 1978. Here we discuss recent advances our understanding this phenomenon relation to novel concepts associated with large-scale chromatin structure during development both axial limb patterns. We further how sequential transcriptional activation marks embryonic stem cell-like progenitors mammals and, consequently, a temporal genetic system is translated into spatial coordinates via fate these progenitors. In context, argue benefit necessity implementing unique mechanism as well difficulty evolving alternative strategy deliver critical positional information.

Language: Английский

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Polycomb and Trithorax Group Genes in Drosophila

Genetics, Journal Year: 2017, Volume and Issue: 206(4), P. 1699 - 1725

Published: Aug. 1, 2017

Abstract Polycomb group (PcG) and Trithorax (TrxG) genes encode important regulators of development differentiation in metazoans. These two groups were discovered Drosophila by their opposing effects on homeotic gene (Hox) expression. PcG collectively behave as genetic repressors Hox genes, while the TrxG are necessary for HOX expression or function. Biochemical studies showed that many proteins present protein complexes, repressive complexes 1 2, which repress transcription via chromatin modifications. activate a variety mechanisms. Here we summarize large body biochemical experiments these genes.

Language: Английский

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Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2

Nature Structural & Molecular Biology, Journal Year: 2018, Volume and Issue: 25(3), P. 225 - 232

Published: Feb. 23, 2018

Language: Английский

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An H3K27me3 demethylase-HSFA2 regulatory loop orchestrates transgenerational thermomemory in Arabidopsis

Cell Research, Journal Year: 2019, Volume and Issue: 29(5), P. 379 - 390

Published: Feb. 18, 2019

Global warming has profound effects on plant growth and fitness. Plants have evolved sophisticated epigenetic machinery to respond quickly heat, exhibit transgenerational memory of the heat-induced release post-transcriptional gene silencing (PTGS). However, how thermomemory is transmitted progeny physiological relevance are elusive. Here we show that HEAT SHOCK TRANSCRIPTION FACTOR A2 (HSFA2) directly activates H3K27me3 demethylase RELATIVE OF EARLY FLOWERING 6 (REF6), which in turn derepresses HSFA2. REF6 HSFA2 establish a heritable feedback loop, activate an E3 ubiquitin ligase, SUPPRESSOR GENE SILENCING 3 (SGS3)-INTERACTING PROTEIN 1 (SGIP1). SGIP1-mediated SGS3 degradation leads inhibited biosynthesis trans-acting siRNA (tasiRNA). The REF6-HSFA2 loop reduced tasiRNA converge HEAT-INDUCED TAS1 TARGET 5 (HTT5), drives early flowering but attenuates immunity. Thus, heat induces phenotypes via coordinated network involving histone demethylases, transcription factors, tasiRNAs, ensuring reproductive success stress adaptation.

Language: Английский

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Targeted reprogramming of H3K27me3 resets epigenetic memory in plant paternal chromatin

Nature Cell Biology, Journal Year: 2020, Volume and Issue: 22(6), P. 621 - 629

Published: May 11, 2020

Language: Английский

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