小柯机器人

南京医科大学，华南肿瘤国家重点实验室、肿瘤医学协同创新中心Jian Zheng，Dongxin Lin和美国希望之城贝克曼研究所Jianjun Chen共同合作，近期取得重要工作进展。他们研究发现RNA m6A通过DNA去甲基化和染色质可及性调控转录。该研究2022年9月7日在线发表于《自然—遗传学》杂志上。

研究人员发现METTL3介导的RNA N6-甲基腺苷（m6A）形成导致正常细胞和癌细胞中附近基因组位点的DNA去甲基化，这是由m6A读取器FXR1和DNA 5-甲基胞嘧啶双加氧酶TET1之间的相互作用介导的。在识别RNA m6A后，FXR1将TET1募集到基因组位点以使DNA去甲基化，从而导致染色质可及性和基因转录的重编程。因此，研究人员描述了由RNA m6A形成和DNA去甲基化介导的染色质可及性和基因转录的调节机制，强调了RNA m6A和DNA修饰之间的相互关联在生理和致病过程中的重要性。

据了解，转录调控整合了染色质可及性、转录因子和表观遗传修饰，对建立和维持细胞特性至关重要。不同的表观遗传修饰之间的相互作用及其对转录调控的贡献仍然是很重要的。

附：英文原文

Title: RNA m6A regulates transcription via DNA demethylation and chromatin accessibility

Author: Deng, Shuang, Zhang, Jialiang, Su, Jiachun, Zuo, Zhixiang, Zeng, Lingxing, Liu, Kaijing, Zheng, Yanfen, Huang, Xudong, Bai, Ruihong, Zhuang, Lisha, Ye, Ying, Li, Mei, Pan, Ling, Deng, Junge, Wu, Guandi, Li, Rui, Zhang, Shaoping, Wu, Chen, Lin, Dongxin, Chen, Jianjun, Zheng, Jian

Issue&Volume: 2022-09-07

Abstract: Transcriptional regulation, which integrates chromatin accessibility, transcription factors and epigenetic modifications, is crucial for establishing and maintaining cell identity. The interplay between different epigenetic modifications and its contribution to transcriptional regulation remains elusive. Here, we show that METTL3-mediated RNA N6-methyladenosine (m6A) formation leads to DNA demethylation in nearby genomic loci in normal and cancer cells, which is mediated by the interaction between m6A reader FXR1 and DNA 5-methylcytosine dioxygenase TET1. Upon recognizing RNA m6A, FXR1 recruits TET1 to genomic loci to demethylate DNA, leading to reprogrammed chromatin accessibility and gene transcription. Therefore, we have characterized a regulatory mechanism of chromatin accessibility and gene transcription mediated by RNA m6A formation coupled with DNA demethylation, highlighting the importance of the crosstalk between RNA m6A and DNA modification in physiologic and pathogenic process.

DOI: 10.1038/s41588-022-01173-1

Source: https://www.nature.com/articles/s41588-022-01173-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex