威廉希尔学术报告
Title: Oncohistones H3.3K36M and H3.3K27M reprogram the epigenome of tumors
演讲人：Dong Fang, Ph.D., 
Associate Research Scientist, 
Institute for Cancer Genetics, 
Columbia University Medical Center
时间：2017年6月6日13:30-14:30
地点：新生物楼311
Abstract:
With the expansion of cancer genome sequencing, many chromatin-regulating genes are found mutated. It’s found that histone proteins, the basic component of epigenetics information, are mutated in a variety of cancers. Specifically, the lysine 27 to methionine (K27M) mutation in histone H3.3 is found in 60% of diffuse intrinsic pontine glioma (DIPG), a high-grade pediatric brain tumor with dismal prognosis. In addition, a somatic histone H3.3K36M mutation is identified in over 90% of chondroblastomas. In human genome, there are 15 genes encoding histone H3 proteins. It is unknown how mutations at only one allele of these 15 histone H3 genes are linked to tumorigenesis. We have shown that the H3.3K27M and H3.3K36M mutations dominantly reprogram H3K27 di- and tri-methylation of (H3K27me2/me3) in DIPG cells and H3K36me2/me3 in chondroblastomas respectively. Mechanistically, we show that these mutant proteins inhibit enzymatic activity of corresponding methyltransferases and subsequently the epigenome and gene expression. Based on these studies, we propose that different histone mutations reprogram epigenome of different progenitor cells, which in turn alters gene expression and transform different progenitor cells.
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