RNA剪接
表观遗传学
串扰
生物
表观基因组
上皮-间质转换
转移
拼接因子
细胞生物学
选择性拼接
基因
遗传学
核糖核酸
DNA甲基化
癌症
外显子
基因表达
光学
物理
作者
Sanjeeb Kumar Sahu,Eneritz Agirre,Mohammed Inayatullah,Arun Mahesh,Neha Tiwari,Deborah Lavin,Aditi Singh,Susanne Strand,Mustafa Diken,Reini F. Luco,Juan Carlos Izpisúa Belmonte,Vijay Tiwari
标识
DOI:10.1038/s41556-022-00971-3
摘要
Epithelial-to-mesenchymal transition (EMT) renders epithelial cells migratory properties. While epigenetic and splicing changes have been implicated in EMT, the mechanisms governing their crosstalk remain poorly understood. Here we discovered that a C2H2 zinc finger protein, ZNF827, is strongly induced during various contexts of EMT, including in brain development and breast cancer metastasis, and is required for the molecular and phenotypic changes underlying EMT in these processes. Mechanistically, ZNF827 mediated these responses by orchestrating a large-scale remodelling of the splicing landscape by recruiting HDAC1 for epigenetic modulation of distinct genomic loci, thereby slowing RNA polymerase II progression and altering the splicing of genes encoding key EMT regulators in cis. Our findings reveal an unprecedented complexity of crosstalk between epigenetic landscape and splicing programme in governing EMT and identify ZNF827 as a master regulator coupling these processes during EMT in brain development and breast cancer metastasis.
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