1、The School of Life Sciences and TechnologyTongji University,果蝇的核小体定位与基因调控,江赐忠,同济大学生命科学与技术学院,2018年9月23日,What is nucleosome?,H2A , H2B , H3 and H4,AcetylationMethylationUbiquinationSumoylationPhosphorylationADP ribosylationDeiminationProline isomerization,DNA,Nucleosome,Chromosome,Modified from Nature
2、 2008, 454:711-715,DNA packaging,Nucleosome and gene regulation,红细胞,神经细胞,小肠表皮细胞,脂肪细胞,平滑肌细胞,One genome, multiple epigenomes,egg,embryo,larva,pupa,adult,Model organism: Drosophila,Methods,Screen shot of browser,Chromosome 3L,Nature 446 (7135):572-6 (2007),TSS,Aggregation of nucleosome positions,Nucleo
3、some organization around TSS,NFR,Aggregation of nucleosome positions,Nucleosome organization around ORF end,NFR,Nucleosomal landscape of genes,5NFR,3NFR,Nat. Rev. Genet. 10(3):161-72 (2009),Paused Pol II,Paused Pol II,Not paused vs. paused genes,+1,Nucleosome shift,gene,+2,+3,+4,+5,Paused Pol II,10,
4、10,10,10,10,Pol II-bound nucleosomes,Pol II,Y,Ab,XL,Immunoprecipitation & DNA purification,Hybridization to tiling array,Mapping probes to genome,Pol II-bound nucleosomes,Pol II,Drosophila vs. yeast,NFR,GAGA motif and GAF,Nucleosome positioning sequences (TSS),Nucleosome positioning sequences (ORF e
5、nd),Nucleosome packing,Nat. Rev. Genet. 10(3):161-72 (2009),Nucleosome during replication,Motifs distribution around nucleosomes,Modified from Chromosome Research (2006) 14:5-16,Modified from Nature (2007) 446:572-576,gene,motif,nucleosome,Arrangement of motifs around TSS and nucleosomes,Genome-wide
6、 motif arrangement,Nucleosomal,Anti-nucleosomal,Fixed,Random,gene,motif,nucleosome,-500 bp,-500 bp,+500 bp,Conclusion,Uniform nucleosome arrangement in genic regionsAn NFR exists at both ends of genesGAF may contribute to lack of -1 nucleosomesRNA polymerase II engages the +1 nucleosome and pauses N
7、on-random motif organization relative to nucleosomes,Dr. Frank PughDr. Istvan AlbertTravis MavrichLynn P. TomshoDr. Ilya IoschikhesDr. Xiaoyong Li,Other lab members,Acknowledgements,同济大学生物信息系,全职正教授,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：基
8、因组学和表观遗传组学Nature (2008), Genome Res (2008), Nat Review Genet (2009) 。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)。,海外团队,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：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：Bayl
9、or医学院，NIH表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,兼职教授和其它,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 哈尔宾医科大学沈百荣 苏州大学刘雷 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,谢谢！,主要表观遗传机制,DNA甲基化组蛋白修饰核小体定位非编码RNA,该酶突变导致： Williams 综合症发育迟缓， 智力发展迟缓 ，早衰，走路笨拙 ，有典型的脸部外观,染色质重塑酶：BRM (brahma),表观遗传调空紊乱导致重大疾病,Nucleoso
10、me organization around TSS,NFR,H2A.Z,Bulk,Nucleosome organization around ORF end,NFR,H2A.Z,Bulk,Fuzziness of nucleosomes,Highly vs. lowly expressed genes,Phased vs. fuzzy,核小体定位的机制不清楚,核小体定位是动态的,染色质重塑,Aggregation of motif positions,Scrambled motifs,gene,motif,nucleosome,-500 bp,-500 bp,+500 bp,ACGTTACT,CAGTTACT,CTGATACT,基因组时代后基因组时代,
