UTX inhibits EMT-induced breast CSC properties by epigenetic repression of EMT genes in cooperation with LSD1 and HDAC1
- Authors
- Choi, Hee-Joo; Park, Ji-Hye; Park, Mikyung; Won, Hee-Young; Joo, Hyeong-seok; Lee, Chang Hoon; Lee, Jeong-Yeon; Kong, Gu
- Issue Date
- Oct-2015
- Publisher
- WILEY
- Keywords
- breast CSC; EMT; UTX
- Citation
- EMBO REPORTS, v.16, no.10, pp.1288 - 1298
- Indexed
- SCIE
SCOPUS
- Journal Title
- EMBO REPORTS
- Volume
- 16
- Number
- 10
- Start Page
- 1288
- End Page
- 1298
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/156250
- DOI
- 10.15252/embr.201540244
- ISSN
- 1469-221X
- Abstract
- The histone H3K27 demethylase, UTX, is a known component of the H3K4 methyltransferase MLL complex, but its functional association with H3K4 methylation in human cancers remains largely unknown. Here we demonstrate that UTX loss induces epithelial-mesenchymal transition (EMT)-mediated breast cancer stem cell (CSC) properties by increasing the expression of the SNAIL, ZEB1 and ZEB2 EMT transcription factors (EMT-TFs) and of the transcriptional repressor CDH1. UTX facilitates the epigenetic silencing of EMT-TFs by inducing competition between MLL4 and the H3K4 demethylase LSD1. EMT-TF promoters are occupied by c-Myc and MLL4, and UTX recognizes these proteins, interrupting their transcriptional activation function. UTX decreases H3K4me2 and H3 acetylation at these promoters by forming a transcriptional repressive complex with LSD1, HDAC1 and DNMT1. Taken together, our findings indicate that UTX is a prominent tumour suppressor that functions as a negative regulator of EMT-induced CSC-like properties by epigenetically repressing EMT-TFs.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 서울 의과대학 > 서울 병리학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/156250)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.