Epigenetics

Alterations of epigenetics including DNA methylation and histone modifications play crucial roles in both initiation and progression of certain types of cancers. Abnormal histone modifications identified within these tumors represent potential biomarkers and therapeutic pathways. In this study, two different types of human hepatocellular carcinoma cell lines HepG2 and MHCC97-H with distinct metastasis capability are used to investigate the association of liver metastasis with cellular histone modification levels. In the HepG2 and MHCC97-H cells, 17 types of histone H3 modification corresponding to methylation are quantitatively profiled with LC coupled to high resolution mass spectrometry. Compared to HepG2 cells without metastasis capability, the combinatorial histone peptides of K9me1K14ac and K9me0K14ac in malignant MHCC97-H cells are found to be significantly down regulated, while the level of H3K9me3 and H3K27me2 are greatly increased. Overall these data provide novel insights into the histone methylation regulatory mechanism in liver metastasis and reveal the epigenetic pathway for HCC disease development. Histone proteins, as well as DNA, are important components of chromatin representing the physiological form of the genome. Nucleosome is the repeating unit of chromatin in which genomic DNA is wrapped around a core octamer consisting of dimers of four histone proteins (H2A, H2B, H3 and H4 and/or their variant isoforms). Another histone protein H1 serves as a linker to further connect individual nucleosomes into larger chromatin fiber. A large variety of post-translational modifications (PTM) are discovered on histones in the last decade. Histone modification, along with DNA methylation, noncoding RNA and chromatin remodeling contribute to the regulation mechanism of epigenetics. Hong Jin, Quantitative Profiling of Histone H3 Methylation in Human Hepatocellular Carcinoma"

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Last date updated on September, 2024