English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule neuron progenitors (CGNPs) and its mis-regulation 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 +/- ; Ptch1 +/- mice showed lower spontaneous MB occurrence compared with Ptch1 +/- 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.

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