学术报告

Title:Broad H3K4me3 Reveals Increased Transcription Elongation and Enhancer Activity at Tumor Suppressors

Speaker: Kaifu Chen

Division of Biostatistics

Department of Molecular and Cellular Biology

Baylor College of Medicine

Time: 13:30-14:30 PM, April 9, 2014 (Thu.)

Venue: Rm. 311, New Life Sciences Building

Tumor suppressors are mostly defined by inactivating somatic mutations in tumors, yet little is known about their epigenetic features in normal cells. Here, through integrative analysis of 1,134 genome-wide epigenetic profiles and mutations from >8,200 tumor-normal pairs, we discovered broad H3K4me3 (wider than 4 kb) as the first epigenetic signature for tumor suppressors in normal cells. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity, which together lead to exceptionally high gene expression. Inhibiting transcription elongation causes H3K4me3 shortening. Broad H3K4me3 conserved across normal cells or tissues represents a set of core tumor suppressors, such as P53 and PTEN, whereas cell-type-specific broad H3K4me3 indicates cell-identity genes and cell-type-specific tumor suppressors. Furthermore, widespread shortening of broad H3K4me3 in cancers is strongly associated with repression of tumor suppressors. Cellular validation indicates that 87.5% of tumor suppressor candidates defined based on conserved broad H3K4me3 sigfinicantly suppress tumor cell growth. Together, the broad H3K4me3 epigenetic signature we reported here provide a new direction for the discovery and characterization of novel tumor suppressors.

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