小柯机器人

美国哈佛医学院David Pellman等研究人员合作发现来自核结构畸变的遗传性转录缺陷。2023年6月7日，《自然》杂志在线发表了这项成果。

研究人员发现微核和染色体桥，即癌症中常见的细胞核畸变，是遗传性转录抑制的来源。研究人员使用多种方法，包括长期活细胞成像和同细胞单细胞RNA测序（Look-Seq2），确定了微核中染色体的基因表达减少。由于具有异质性，这些基因表达的变化甚至在微核的染色体被重新整合到正常的子细胞核中之后也可以遗传。同时，微核染色体获得异常的表观遗传染色质标记。这些缺陷可能持续为染色质可及性不同程度的降低，以及从单细胞克隆扩增后的基因表达减少。持续的转录抑制与明显的长效DNA损伤密切相关，并可由其解释。因此，转录的表观遗传学改变可能与染色体不稳定和核结构畸变有着内在的联系。

据介绍，染色质表观遗传状态的可塑性导致的转录异质性有助于肿瘤的演变、转移和抗药性。然而，导致这种表观遗传变异的机制并不完全了解。

附：英文原文

Title: Heritable transcriptional defects from aberrations of nuclear architecture

Author: Papathanasiou, Stamatis, Mynhier, Nikos A., Liu, Shiwei, Brunette, Gregory, Stokasimov, Ema, Jacob, Etai, Li, Lanting, Comenho, Caroline, van Steensel, Bas, Buenrostro, Jason D., Zhang, Cheng-Zhong, Pellman, David

Issue&Volume: 2023-06-07

Abstract: Transcriptional heterogeneity due to plasticity of the epigenetic state of chromatin contributes to tumour evolution, metastasis and drug resistance1,2,3. However, the mechanisms that cause this epigenetic variation are incompletely understood. Here we identify micronuclei and chromosome bridges, aberrations in the nucleus common in cancer4,5, as sources of heritable transcriptional suppression. Using a combination of approaches, including long-term live-cell imaging and same-cell single-cell RNA sequencing (Look-Seq2), we identified reductions in gene expression in chromosomes from micronuclei. With heterogeneous penetrance, these changes in gene expression can be heritable even after the chromosome from the micronucleus has been re-incorporated into a normal daughter cell nucleus. Concomitantly, micronuclear chromosomes acquire aberrant epigenetic chromatin marks. These defects may persist as variably reduced chromatin accessibility and reduced gene expression after clonal expansion from single cells. Persistent transcriptional repression is strongly associated with, and may be explained by, markedly long-lived DNA damage. Epigenetic alterations in transcription may therefore be inherently coupled to chromosomal instability and aberrations in nuclear architecture.

DOI: 10.1038/s41586-023-06157-7

Source: https://www.nature.com/articles/s41586-023-06157-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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