genome-wide integration on transcription factors, histone acetylation and gene expression reveals genes co-regulated by histone modification patterns全基因组整合转录因子,组蛋白乙酰化组蛋白的化学修饰和基因表达揭示基因重新模式.pdfVIP

Genome-Wide Integration on Transcription Factors, Histone Acetylation and Gene Expression Reveals Genes Co-Regulated by Histone Modification Patterns Yayoi Natsume-Kitatani1,2¤, Motoki Shiga1,2, Hiroshi Mamitsuka1,2* 1 Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Japan, 2 Institute for Bioinformatics Research and Development of Japan Science and Technology Agency (JST-BIRD), Saitama, Japan Abstract N-terminal tails of H2A, H2B, H3 and H4 histone families are subjected to posttranslational modifications that take part in transcriptional regulation mechanisms, such as transcription factor binding and gene expression. Regulation mechanisms under control of histone modification are important but remain largely unclear, despite of emerging datasets for comprehensive analysis of histone modification. In this paper, we focus on what we call genetic harmonious units (GHUs), which are co-occurring patterns among transcription factor binding, gene expression and histone modification. We present the first genome-wide approach that captures GHUs by combining ChIP-chip with microarray datasets from Saccharomyces cerevisiae. Our approach employs noise-robust soft clustering to select patterns which share the same preferences in transcription factor-binding, histone modification and gene expression, which are all currently implied to be closely correlated. The detected patterns are a well-studied acetylation of lysine 16 of H4 in glucose depletion as well as co- acetylation of five lysine residues of H3 with H4 Lys12 and H2A Lys7 responsible for ribosome biogenesis. Furthermore, our method further suggested the recognition of acetylated H4 Lys16 being crucial to histone acetyltransferase ESA1, whose essential role is still under controversy, from a mic