| Literature DB >> 35941369 |
Eneritz Agirre1,2, Mohammed Inayatullah3, Sanjeeb Kumar Sahu4,5, Arun Mahesh3, Neha Tiwari6, Deborah P Lavin3, Aditi Singh3, Susanne Strand7, Mustafa Diken8, Reini F Luco1, Juan Carlos Izpisua Belmonte4,5, Vijay K Tiwari9.
Abstract
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.Entities:
Mesh：
Year: 2022 PMID： 35941369 DOI： 10.1038/s41556-022-00971-3
Source DB: PubMed Journal: Nat Cell Biol ISSN： 1465-7392 Impact factor: 28.213