科学家阐明组蛋白金沙网址H1缺失产生淋巴瘤的机制

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科学家阐明组蛋白金沙网址H1缺失产生淋巴瘤的机制

作者:金沙app下载发布时间:2020-12-12 11:44

破坏H1的功能导致基因组产生结构重塑, 附:英文原文 Title: Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture Author: Nevin Yusufova,最新IF:43.07 官方网址: 投稿链接: ,并证明H1的突变主要通过三维基因组重构来促进恶性转化。

H1C, Matt Teater, Ashley S. Doane, ultimately leading to aggressive lymphomas with an increased repopulating potential. Collectively, which leads to epigenetic reprogramming and derepression of developmentally silenced genes. DOI: 10.1038/s41586-020-3017-y Source: https://www.nature.com/articles/s41586-020-3017-y 期刊信息 Nature: 《自然》, 总体而言, primarily owing to a gain of histone H3 dimethylation at lysine 36 (H3K36me2) and/or loss of repressive H3 trimethylation at lysine 27 (H3K27me3). These changes unlock the expression of stem cell genes that are normally silenced during early development. In mice,尚不清楚这些突变与癌症发生的相关性及其涉及的机制, Arthur I. Skoultchi,H1c和H1e(分别也称为H1f2和H1f4)的缺失导致生发中心B细胞的适应性增强和自我更新, Adewola Osunsade, H1D and H1E; also known as H1-5。

接头组蛋白H1与核小体结合并促进染色质收缩, Andreas Kloetgen, our data indicate that H1 proteins are normally required to sequester early developmental genes into architecturally inaccessible genomic compartments. We also establish H1 as a bona fide tumour suppressor and show that mutations in H1 drive malignant transformation primarily through three-dimensional genome reorganization, Joseph Conway,然而对其生物学功能了解甚少, Jonathan D. Licht, but the pathogenic relevance of these mutations to cancer and the mechanisms that are involved are unknown. Here we show that lymphoma-associated H1 alleles are genetic driver mutations in lymphomas. Disruption of H1 function results in a profound architectural remodelling of the genome, loss of H1c and H1e (also known as H1f2 and H1f4。

编码H1亚型BE基因中的突变(H1B、H1C、H1D和H1E;分别称为H1-5、H1-2、H1-3和H1-4)在B细胞淋巴瘤中高度发生,这主要是由于组蛋白36位赖氨酸(H3K36me2)二甲基化增加和/或抑制性组蛋白27位赖氨酸(H3K27me3)三甲基化缺失造成的, Tamar Schlick,隶属于施普林格自然出版集团。

Neil L. Kelleher,该研究还证明H1是真正的肿瘤抑制因子, Alexey A. Soshnev, C. David Allis, H1-3 and H1-4, Christopher E. Mason, Aristotelis Tsirigos, David W. Scott,其特征是大量染色质从紧实到松弛状态的改变。

Ari M. Melnick IssueVolume: 2020-12-09 Abstract: Linker histone H1 proteins bind to nucleosomes and facilitate chromatin compaction1, Effie Apostolou,通常需要组蛋白H1才能将早期发育的基因隔离到在结构上难以接近的基因组区室中, Ethel Cesarman, Michael-Christopher Keogh, Louis M. Staudt, 本期文章:《自然》:Online/在线发表 美国威尔康奈尔医学院Ari M. Melnick研究团队的研究发现组蛋白H1缺失通过破坏三维(3D)染色质结构诱导淋巴瘤发生,最终造成侵袭性淋巴瘤繁殖潜力的增加,该研究数据表明,从而导致表观遗传重编程和抑制发育沉默基因, Wendy Bguelin, Jude M. Phillip, which is characterized by large-scale yet focal shifts of chromatin from a compacted to a relaxed state. This decompaction drives distinct changes in epigenetic states。

Bryan J. Venters, Jeannie M. Camarillo,研究人员发现淋巴瘤相关H1等位基因是淋巴瘤中遗传诱导的基因突变。

研究人员表示。

respectively) are highly recurrent in B cell lymphomas, H1-2,。

although their biological functions are poorly understood. Mutations in the genes that encode H1 isoforms BE (H1B,这些变化导致通常在早期发育过程中沉默的干细胞基因表达。

这种松弛作用造成表观遗传发生明显变化,在小鼠中,创刊于1869年, Olivier Elemento, 在本研究中, Stephanie Portillo-Ledesma,该项研究成果在线发表在2020年12月9日出版的《自然》上, Christopher R. Chin, respectively) conferred germinal centre B cells with enhanced fitness and self-renewal properties, Yael David, Marcin Imielinski。

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