果蝇的核小体定位与基因调控

1、The School of Life Sciences and TechnologyTongji University江赐忠同济大学生命科学与技术学院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曹志伟曹志伟：中医药信息学和免疫信息学 40余篇SCI论文：Pharmacological Reviews, Nature reviews drug discovery, PNAS，MCP, NAR等。江赐忠江赐忠：基因组学和表观遗传组学 Nature

8、 (2008), Genome Res (2008), Nat Review Genet (2009) 。张勇张勇：生物信息学和表观遗传组学 Genome Biol (2008), Genes Dev (2008), Nat Struct Mol Biol (2009)。刘小乐刘小乐：Dana-Farber肿瘤研究所，哈佛大学 转录和表观遗传组学 12篇Nature/Cell系列李程李程：Dana-Farber肿瘤研究所，哈佛大学 生物信息学、计算基因组学和在癌症和神经科学领域的应用 3篇Nature系列, BMC Bioinformatics, 2008李蔚李蔚：Baylor医学院，NIH表

9、观遗传生物信息中心 基因组学，转录和表观遗传组学 9篇Nature/Cell系列 李亦学李亦学 上海生物信息学中心，上海生命科学院，上海交通大学 李霞李霞 哈尔宾医科大学 沈百荣沈百荣 苏州大学 刘雷刘雷 上海生物信息学中心 生物信息本科，硕士，博士专业973，863项目Computer ClusterIllumina高通量测序仪主要表观遗传机制表观遗传调空紊乱导致重大疾病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核小体定位的机制不清楚Aggregation of motif positions123456789ABCDEFTSSScrambled motifsNucleosomalA