Characteristics of H3 K27M-mutant gliomas in adults

Neuro-Oncology, Год журнала: 2016, Номер 19(8), С. 1127 - 1134

Опубликована: Ноя. 3, 2016

Diffuse H3 K27M-mutant gliomas occur primarily in children but can also be encountered adults. The aim of this study was to describe the characteristics We analyzed 21 adult and compared them with those 135 diffuse without histone isocitrate dehydrogenase (IDH) mutation (IDH/H3 wild type). median age at diagnosis 32 years (range: 18–82 y). All tumors had a midline location (spinal cord n = 6, thalamus 5, brainstem cerebellum 3, hypothalamus 1, pineal region 1) were IDH BRAF-V600E type. identification an K27M significantly impacted 3 patients (14%) for whom histological aspect initially suggested low-grade glioma 7 (33%) pathological analysis hesitated between glioma, ganglioglioma, or pilocytic astrocytoma. Compared IDH/H3 wild-type gliomas, diagnosed earlier (32 vs 64 y, P < .001), always (21/21 21/130, less frequently methylated MGMT promoter (1/21 52/129, .002), lacked EGFR amplification (0/21 26/128, .02). survival 19.6 months 17 (P .3). In adults, as children, mutations define distinct subgroup characterized by constant location, low rate methylation, poor prognosis.

Язык: Английский

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Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression

Cancer Cell, Год журнала: 2018, Номер 35(1), С. 140 - 155.e7

Опубликована: Дек. 27, 2018

Язык: Английский

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PRC2 is high maintenance

Genes & Development, Год журнала: 2019, Номер 33(15-16), С. 903 - 935

Опубликована: Май 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.

Язык: Английский

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Histones: At the Crossroads of Peptide and Protein Chemistry

Chemical Reviews, Год журнала: 2014, Номер 115(6), С. 2296 - 2349

Опубликована: Окт. 20, 2014

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTHistones: At the Crossroads of Peptide and Protein ChemistryManuel M. Müller Tom W. Muir*View Author Information Department Chemistry, Princeton University, Frick Laboratory, Princeton, New Jersey 08544, United States*E-mail: [email protected]Cite this: Chem. Rev. 2015, 115, 6, 2296–2349Publication Date (Web):October 20, 2014Publication History Received2 July 2014Published online20 October inissue 25 March 2015https://doi.org/10.1021/cr5003529Copyright © 2014 American Chemical SocietyRIGHTS & PERMISSIONSACS AuthorChoiceArticle Views11913Altmetric-Citations161LEARN ABOUT THESE METRICSArticle Views are COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated to reflect usage leading up last few days.Citations number other articles citing this article, calculated by Crossref daily. Find more information about citation counts.The Altmetric Attention Score is a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence for given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InReddit (21 MB) Get e-AlertsSUBJECTS:Genetics,Modification,Monomers,Organic reactions,Peptides proteins e-Alerts

Язык: Английский

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Assessing sufficiency and necessity of enhancer activities for gene expression and the mechanisms of transcription activation

Genes & Development, Год журнала: 2018, Номер 32(3-4), С. 202 - 223

Опубликована: Фев. 1, 2018

Enhancers are important genomic regulatory elements directing cell type-specific transcription. They assume a key role during development and disease, their identification functional characterization have long been the focus of scientific interest. The advent next-generation sequencing clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based genome editing has revolutionized means by which we study enhancer biology. In this review, cover recent developments in prediction enhancers based on chromatin characteristics reporter assays endogenous DNA perturbations. We discuss that two latter approaches provide different complementary insights, especially assessing sufficiency necessity for transcription activation. Furthermore, insights into mechanistic aspects function, including findings about cofactor requirements post-translational histone modifications such as monomethylation H3 Lys4 (H3K4me1). Finally, survey how these advance our understanding regulation with respect to promoter specificity transcriptional bursting an outlook covering open questions promising developments.

Язык: Английский

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Chromatin signatures of cancer

Genes & Development, Год журнала: 2015, Номер 29(3), С. 238 - 249

Опубликована: Фев. 1, 2015

Changes in the pattern of gene expression play an important role allowing cancer cells to acquire their hallmark characteristics, while genomic instability enables genetic alterations that promote oncogenesis. Chromatin plays central roles both transcriptional regulation and maintenance stability. Studies by genome consortiums have identified frequent mutations genes encoding chromatin regulatory factors histone proteins human cancer, implicating them as major mediators pathogenesis hematological malignancies solid tumors. Here, we review recent advances our understanding focusing on complexes, enhancer-associated factors, point mutations, heterochromatin-interacting factors.

Язык: Английский

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Germ line–inherited H3K27me3 restricts enhancer function during maternal-to-zygotic transition

Science, Год журнала: 2017, Номер 357(6347), С. 212 - 216

Опубликована: Июль 14, 2017

Gametes carry parental genetic material to the next generation. Stress-induced epigenetic changes in germ line can be inherited and have a profound impact on offspring development. However, molecular mechanisms consequences of transgenerational inheritance are poorly understood. We found that Drosophila oocytes transmit repressive histone mark H3K27me3 their offspring. Maternal contribution methyltransferase Enhancer zeste, enzymatic component Polycomb complex 2, is required for active propagation during early embryogenesis. embryo prevents aberrant accumulation H3K27ac at regulatory regions precocious activation lineage-specific genes zygotic genome activation. Disruption line-inherited memory causes embryonic lethality cannot rescued by late reestablishment H3K27me3. Thus, maternally H3K27me3, propagated embryo, regulates enhancers

Язык: Английский

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Chromatin regulatory mechanisms and therapeutic opportunities in cancer

Nature Cell Biology, Год журнала: 2018, Номер 21(2), С. 152 - 161

Опубликована: Дек. 21, 2018

Язык: Английский

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HP1 drives de novo 3D genome reorganization in early Drosophila embryos

Nature, Год журнала: 2021, Номер 593(7858), С. 289 - 293

Опубликована: Апрель 14, 2021

Abstract Fundamental features of 3D genome organization are established de novo in the early embryo, including clustering pericentromeric regions, folding chromosome arms and segregation chromosomes into active (A-) inactive (B-) compartments. However, molecular mechanisms that drive remain unknown 1,2 . Here, by combining conformation capture (Hi-C), chromatin immunoprecipitation with high-throughput sequencing (ChIP–seq), DNA fluorescence situ hybridization (3D FISH) polymer simulations, we show heterochromatin protein 1a (HP1a) is essential for during Drosophila development. The binding HP1a at required to establish regions. Moreover, within responsible overall has an important role formation B-compartment depletion does not affect A-compartment, which suggests a different mechanism segregates Our work identifies as epigenetic regulator involved establishing global structure embryo.

Язык: Английский

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Mechanisms of Polycomb group protein function in cancer

Cell Research, Год журнала: 2022, Номер 32(3), С. 231 - 253

Опубликована: Янв. 19, 2022

Cancer arises from a multitude of disorders resulting in loss differentiation and stem cell-like phenotype characterized by uncontrolled growth. Polycomb Group (PcG) proteins are members multiprotein complexes that highly conserved throughout evolution. Historically, they have been described as essential for maintaining epigenetic cellular memory locking homeotic genes transcriptionally repressed state. What was initially thought to be function restricted few target genes, subsequently turned out much broader relevance, since the main role PcG is ensure dynamically choregraphed spatio-temporal regulation their numerous during development. Their ability modify chromatin landscapes refine expression master controlling major switches decisions under physiological conditions often misregulated tumors. Surprisingly, functional implication initiation progression cancer may either dependent on complexes, or specific subunit acts independently other members. In this review, we describe how play pleiotropic altering broad spectrum biological processes such proliferation-differentiation balance, metabolism immune response, all which crucial tumor progression. We also illustrate interfering with functions can provide powerful strategy counter

Язык: Английский

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