Histone methylation patterns in human breast cancer

Histone post‐translational modifications regulate gene expression, and their misregulation is linked to cancer development. Histone methylation occurs on lysine residues, established by enzymes that regulate chromatin structure and gene activity. The ability of histone methylation to signal in chromatin depends on the lysine that is targeted and the methylation state (me1, me2, or me3) that is achieved. Methylation on histone H3 lysine 4 (H3K4) correlates with gene activity and the H3K4 methyltransferase MLL is translocated in hematological cancers. The H3K36 methyltransferase NSD1 is fused to NUP98 in leukemia and this histone mark is associated with active genes. The pattern of histone modification disruption in cancer has been largely unexplored. We examined by western blot the levels of H3K4me3 and H3K36me3 in breast cancer cell lines. We show that there are differential levels of histone methylation in several of the cancer cell lines when compared to a normal mammary epithelial cell line. BT549 and SUM102 cells exhibit low levels of H3K4me3 and increased levels of H3K36me3. These cell lines also have a defect in DNA methyltransferase activity resulting in increased levels of DNA methylation. Our data suggests that similar to DNA methylation, these histone marks are coupled to the pathology of breast cancer. Future studies will determine if histone methylation marks are clinically relevant for patient assessment.