Insight into Skin Tumorigenesis Highlighting the Function of Epigenetic Regulators in SCC Formation
Abstract
Skin squamous cell carcinoma (sSCC) is one of the most common cancers worldwide. Chromatin regulators have recently emerged as one of the key players in tumorigenesis. Ezh2 is an essential component of the Polycomb complex that represses genes by compacting chromatin. Human genomics studies have shown that Ezh2 is overexpressed in epithelial cancers. Though it has been well accepted that Ezh2 repressive mechanisms depend on catalyzing H3K27me3, the key repressive histone modification mark, our data demonstrates that Ezh2 functions independently of H3K27me3. We found that Ezh2 expression decreased during calcium induced keratinocyte differentiation whereas H3K27me3 did not change. In addition, binding of Ezh2 at differentiation genes dramatically decreased while H3K27me3 maintained a sustained level of enrichment. Importantly ablation of Jmjd3 and UTX in the epidermis results in no obvious skin defects. On the other hand we have found that Ezh2 interacts with Fra2, which is one of important transcription factors in the AP1 family. Our findings suggest that Ezh2 may function in multiple ways to form a regulatory network and imply a new unexpected H3K27me3-independent mechanism. Deep understanding of this fundamental question will shed light on SCC formation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA599253
Entities
People
- Jisheng Zhang
Organizations
- Icahn School of Medicine at Mount Sinai