果蠅的核小體定位與基因調(diào)控

1、The School of Life Sciences and TechnologyTongji University江賜忠同濟大學生命科學與技術學院2022年2月21日What is nucleosome?H2A , H2B , H3 and H41. Acetylation2. Methylation3. Ubiquination4. Sumoylation5. Phosphorylation6. ADP ribosylation7. Deimination8. Proline isomerizationDNANucleosomeChromosomeModified from Nature

2、 2008, 454:711-715DNA packagingNucleosome and gene regulationOne genome, multiple epigenomeseggembryolarvapupaadultModel organism: DrosophilaMethodsScreen shot of browserChromosome 3LTSSAggregation of nucleosome positionsNucleosome organization around TSSgene+1+2+3+4+5NFRAggregation of nucleosome po

3、sitions123456789ABCDEFORF endNucleosome organization around ORF endgeneNFRNucleosomal landscape of genes5NFR3NFRNat. Rev. Genet. 10(3):161-72 (2009)Paused Pol IIgene+1+2+3+4+5Paused Pol IINot paused vs. paused genesgene+1+2+3+4+5+1Nucleosome shiftgene+1+2+3+4+5gene+2+3+4+5Paused Pol II1010101010Pol

4、II-bound nucleosomesPol IIYAbXLImmunoprecipitation & DNA purificationHybridization to tiling arrayMapping probes to genomePol II-bound nucleosomesgene+1+2+3+4+5Pol IIDrosophila vs. yeastNFRgene+1+2+3+4+5-1GAGA motif and GAFGAGAGGgene+1+2+3+4+5GAFNucleosome positioning sequences (TSS)Nucleosome p

5、ositioning sequences (ORF end)Nucleosome packingNat. Rev. Genet. 10(3):161-72 (2009)Nucleosome during replicationMotifs distribution around nucleosomesModified from Chromosome Research (2006) 14:5-16Modified from Nature (2007) 446:572-576genemotifnucleosomeArrangement of motifs around TSS and nucleo

6、somesGenome-wide motif arrangementNucleosomalAnti-nucleosomalFixedRandomgenemotifnucleosome-500 bp-500 bp+500 bp10-1Conclusion Uniform nucleosome arrangement in genic regions An NFR exists at both ends of genes GAF may contribute to lack of -1 nucleosomes RNA polymerase II engages the +1 nucleosome

7、and pauses Non-random motif organization relative to nucleosomesDr. Frank PughDr. Istvan AlbertTravis MavrichLynn P. TomshoDr. Ilya IoschikhesDr. Xiaoyong LiOther lab members曹志偉曹志偉：中醫(yī)藥信息學和免疫信息學 40余篇SCI論文：Pharmacological Reviews, Nature reviews drug discovery, PNAS，MCP, NAR等。江賜忠江賜忠：基因組學和表觀遺傳組學 Nature

8、 (2008), Genome Res (2008), Nat Review Genet (2009) 。張勇張勇：生物信息學和表觀遺傳組學 Genome Biol (2008), Genes Dev (2008), Nat Struct Mol Biol (2009)。劉小樂劉小樂：Dana-Farber腫瘤研究所，哈佛大學 轉(zhuǎn)錄和表觀遺傳組學 12篇Nature/Cell系列李程李程：Dana-Farber腫瘤研究所，哈佛大學 生物信息學、計算基因組學和在癌癥和神經(jīng)科學領域的應用 3篇Nature系列, BMC Bioinformatics, 2008李蔚李蔚：Baylor醫(yī)學院，NIH表

9、觀遺傳生物信息中心 基因組學，轉(zhuǎn)錄和表觀遺傳組學 9篇Nature/Cell系列 李亦學李亦學 上海生物信息學中心，上海生命科學院，上海交通大學 李霞李霞 哈爾賓醫(yī)科大學 沈百榮沈百榮 蘇州大學 劉雷劉雷 上海生物信息學中心 生物信息本科，碩士，博士專業(yè)973，863項目Computer ClusterIllumina高通量測序儀主要表觀遺傳機制表觀遺傳調(diào)空紊亂導致重大疾病Nucleosome organization around TSSNFRgene+1+2+3+4+5-1H2A.ZBulkNucleosome organization around ORF endgeneNFRH2A.ZBulkFuzziness of nucleosomesgene+1+2+3+4+5Highly vs. lowly expressed genesgene+1+2+3+4+5Phased vs. fuzzy核小體定位的機制不清楚Aggregation of motif positions123456789ABCDEFTSSScrambled motifsNucleosomalA