KDM6B is just your average histone demethylase that usually goes about its business stripping methyl marks from H3K27me3 without any drama. That is, until it gets a little out of control and starts demethylating genes associated with Hodgkin’s Lymphoma (HL).
Scientists at the University of Birmingham, UK were looking into the role of H3K27 demethylation in carcinogenesis which led them to KDM6B. Initial research found that the demthylase is critical in normal differentiation, but the team wondered if the mild-mannered KDM6B’s behavior could be negatively influenced by an oncogenic virus like Epstein-Barr (EBV), which is linked to Hodgkin’s Lymphoma. Here’s what they discovered:
- EBV infection of B-cells leads to over-expression of KDM6B
- LMP1, an EBV oncogene, transcriptionally upregulates KDM6B
- KDM6B is over-expressed in primary HL tissue
- Array data matched KDM6B transcriptional targets with genes that are differentially expressed in HL
- Knockdown of KDM6B restored H3K27me3 marks to critical genes like CD58 and NOTCH2NL
So it seems like EBV triggers KDM6B to become a bit over-zealous in its demethylating duties (we’re not judging) causing certain genes to be expressed more than they should, and potentially leading to HL pathogenesis.
With some questions still outstanding, the researchers still aren’t sure if KDM6B is a major culprit or just a small cog in the Hodgkin’s machine.
Figure out if KDM6B is rotten to the core, or just misunderstood at Oncogene, January 2011.