Oncogenic epigenetic control

contributes significantly to the fidelity of biological control. Compromised epigenetic pathways have now been shown to provide indications of transformation and tumor progression; they suggest potential targets for cancer prevention and intervention [1]. A formidable challenge is to deconvolute the complexity and plasticity of histone modifications associated with tumorigenesis. Although challenging, identification of epigenetic signals that are functionally associated with oncogenesis will provide a better understanding of the mechanisms underlying their impact. Post translational modifications of histone3 lysine4 (H3K4) may constitute epigenetically mediated regulatory signatures that can be informative for the molecular characterization of breast cancer pathology. Both methylation and acetylation of H3K4 are associated with gene activation. Tri-methylation of histone3 lysine4 has been extensively studied and is a well-documented marker for active or poised gene transcription. The enzyme complexes that regulate H3K4me3 have been implicated in tumorigenesis, pointing to the relevance of this epigenetic modification in cancer. Histone acetylation as well as histone acetyltransferases and deacetylating enzymes are recognized as important in tumor progression. However, the acetylation of H3K4 in particular has been less extensively investigated to date. Messier, et al., addressed the coordinated contributions of H3K4me3 and H3K4ac to breast cancer tumorigenesis in three well-established human mammary cell lines that represent a normal-like subtype (MCF10A; fibrocystic disease) and two cancer subtypes, luminal (MCF7; ER+/PR+) and basal-like metastatic (MDA-MB-231; ER-/PR-/HER2-) [2]. These cell lines recapitulate the phenotypic and proliferative transitions that accompany tumor progression states. Utilizing ChIP-seq analysis, a genome-wide map of H3K4me3 and H3K4ac patterns was developed, establishing dynamic alterations in the overall histone H3K4 epigenetic landscape in the three cell lines. An observed global increase in H3K4ac in MCF7 and MDA-MB-231 cell lines that is accompanied by a global increase in H3K4me3 in the MDA-MB-231 metastatic cell line is consistent with increased representation of both histone marks during Letters to the Editors oncogenic progression. Modifications in H3K4 tri-methylation and acetylation were found to occur on specific chromosomes, including the X-chromosome. This striking change in H3K4 tri-methylation and acetylation may account for the loss of X-chromosome inactivation and epigenomic instability of the inactive X-chromosome seen in breast cancer [3]. In contrast to methylation and acetylation of H3K9 and H3K27, which activate or repress transcription respectively, methylation and acetylation of H3K4 are both associated with gene activation. Observed increases in H3K4 acetylation marks at specific gene promoters in both the MCF7 and MDA-MB-231 cell lines, compared to normal-like MCF10A …