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RNF220 is required for cerebellum development and regulates medulloblastoma progression through epigenetic modulation of Shh signaling.

RNF220 is required for cerebellum development and regulates medulloblastoma progression through epigenetic modulation of Shh signaling.

Authors :
Pengcheng Ma
Tao An
Liang Zhu
Longlong Zhang
Huishan Wang
Biyu Ren
Bin Sun
Xia Zhou
Yan Li
Bingyu Mao
Source :
Development (09501991); Nov2020, Vol. 147 Issue 23, p1-12, 12p
Publication Year :
2020

Abstract

Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule neuron progenitors (CGNPs) and its misregulation is linked to various disorders, including the cerebellar cancer medulloblastoma (MB). We recently identified RNF220, a ubiquitin E3 ligase promoting K63-linked polyubiquitylation and nuclear exportation of Gli transcription factors, as an Shh/Gli regulator involved in ventral neural patterning. Here, we report that RNF220 is required for the proliferation of CGNPs and Daoy cells (an Shh-grouped MB cell line), working as a positive regulator of Shh signaling. Mechanistic investigation demonstrated that RNF220 promotes Shh target gene expression by targeting the PRC2 component EED, and alters levels of epigenetic modification marks on Shh target promoters. We provided evidence that RNF220<superscript>+/-</superscript>; Ptch1<superscript>+/-</superscript> mice showed lower spontaneous MB occurrence compared with Ptch1<superscript>+/-</superscript> mice. Furthermore, in human clinical MB samples, RNF220 expression correlated well with that of GAB1, an Shh-group MB marker. Our findings provide new insights into the epigenetic regulation of Shh signaling and identify RNF220 as a potential new diagnostic marker and therapeutic target for Shh-group MB [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09501991
Volume :
147
Issue :
23
Database :
Complementary Index
Journal :
Development (09501991)
Publication Type :
Academic Journal
Accession number :
150566277
Full Text :
https://doi.org/10.1242/dev.188078