TY - JOUR
T1 - The H3K27me3 demethylase, KDM6B, is induced by Epstein-Barr virus and over-expressed in Hodgkin's Lymphoma
AU - Anderton, J A
AU - Bose, S
AU - Vockerodt, M
AU - Vrzalikova, K
AU - Wei, W
AU - Kuo, M
AU - Helin, K
AU - Christensen, Jesper Aagaard
AU - Rowe, M
AU - Murray, P G
AU - Woodman, C B
PY - 2011/4/28
Y1 - 2011/4/28
N2 - There is now evidence for both increased and decreased activity of the enzymes controlling the methylation of lysine 27 on histone 3 (H3K27) in cancer. One of these enzymes, KDM6B formally known as JMJD3, a histone demethylase, which removes the trimethyl mark from H3K27, is required for the lineage commitment and terminal differentiation of neural stem cells and of keratinocytes. Our results suggest that KDM6B may also have a role in antigen-driven B-cell differentiation. KDM6B expression increases in B-cell subsets with increasing stage of differentiation, and gene expression profiling shows that KDM6B transcriptional targets in germinal centre B (GC B) cells are significantly enriched for those differentially expressed during memory and plasma cell differentiation. Our results also suggest that aberrant expression of KDM6B may contribute to the pathogenesis of Hodgkin's Lymphoma (HL), an Epstein-Barr virus (EBV) associated malignancy. KDM6B is over-expressed in primary HL and induced by the EBV oncogene, latent membrane protein (LMP1) in GC B cells, the presumptive progenitors of HL. Consistent with these observations, we found that KDM6B transcriptional targets in GC B cells are enriched for genes differentially expressed in HL, and that KDM6B depletion can restore the tri-methylation of H3K27 on these genes.
AB - There is now evidence for both increased and decreased activity of the enzymes controlling the methylation of lysine 27 on histone 3 (H3K27) in cancer. One of these enzymes, KDM6B formally known as JMJD3, a histone demethylase, which removes the trimethyl mark from H3K27, is required for the lineage commitment and terminal differentiation of neural stem cells and of keratinocytes. Our results suggest that KDM6B may also have a role in antigen-driven B-cell differentiation. KDM6B expression increases in B-cell subsets with increasing stage of differentiation, and gene expression profiling shows that KDM6B transcriptional targets in germinal centre B (GC B) cells are significantly enriched for those differentially expressed during memory and plasma cell differentiation. Our results also suggest that aberrant expression of KDM6B may contribute to the pathogenesis of Hodgkin's Lymphoma (HL), an Epstein-Barr virus (EBV) associated malignancy. KDM6B is over-expressed in primary HL and induced by the EBV oncogene, latent membrane protein (LMP1) in GC B cells, the presumptive progenitors of HL. Consistent with these observations, we found that KDM6B transcriptional targets in GC B cells are enriched for genes differentially expressed in HL, and that KDM6B depletion can restore the tri-methylation of H3K27 on these genes.
KW - B-Lymphocyte Subsets
KW - Cell Differentiation
KW - Cell Line, Tumor
KW - Cell Transformation, Viral
KW - Gene Expression Regulation, Neoplastic
KW - Herpesvirus 4, Human
KW - Hodgkin Disease
KW - Humans
KW - Jumonji Domain-Containing Histone Demethylases
KW - Transcription, Genetic
KW - Up-Regulation
KW - Viral Matrix Proteins
U2 - 10.1038/onc.2010.579
DO - 10.1038/onc.2010.579
M3 - Journal article
C2 - 21242977
SN - 0950-9232
VL - 30
SP - 2037
EP - 2043
JO - Oncogene
JF - Oncogene
IS - 17
ER -
