Ho JWK*, Jung YL*, Liu T*, Alver BH, Lee S, Ikegami K, Sohn K-A, Minoda A, Tolstorukov MY, Appert A, Parker SCJ, Gu T, Kundaje A, Riddle NC, Bishop EP, Egelhofer TA, Hu S'en S, Alekseyenko AA, Rechtsteiner A, Asker D, Belsky JA, Bowman SK, Chen BQ, Chen RA-J, Day DS, Dong Y, Dose AC, Duan X, Epstein CB, Ercan S, Feingold EA, Ferrari F, Garrigues JM, Gehlenborg N, Good PJ, Haseley P, He D, Herrmann M, Hoffman MM, Jeffers TE, Kharchenko PV, Kolasinska-Zwierz P, Kotwaliwale CV, Kumar N, Langley SA, Larschan EN, Latorre I, Libbrecht MW, Lin X, Park R, Pazin MJ, Pham HN, Plachetka A, Qin B, Schwartz YB, Shoresh N, Stempor P, Vielle A, Wang C, Whittle CM, Xue H, Kingston RE, Kim JH, Bernstein BE, Dernburg AF, Pirrotta V, Kuroda MI, Noble WS, Tullius TD, Kellis M, MacAlpine DM**, Strome S**, Elgin SCR**, Liu XS**, Lieb JD**, Ahringer J**, Karpen GH**, Park PJ**.
Comparative analysis of metazoan chromatin organization. Nature 2014;512(7515):449-52.
Abstract
Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
pdf Gerstein MB* **, Rozowsky J*, Yan K-K*, Wang D*, Cheng C*, Brown JB*, Davis CA*, Hillier LD*, Sisu C*, Li JJ*, Pei B*, Harmanci AO*, Duff MO*, Djebali S*, Alexander RP, Alver BH, Auerbach R, Bell K, Bickel PJ, Boeck ME, Boley NP, Booth BW, Cherbas L, Cherbas P, Di C, Dobin A, Drenkow J, Ewing B, Fang G, Fastuca M, Feingold EA, Frankish A, Gao G, Good PJ, Guigó R, Hammonds A, Harrow J, Hoskins RA, Howald C, Hu L, Huang H, Hubbard TJP, Huynh C, Jha S, Kasper D, Kato M, Kaufman TC, Kitchen RR, Ladewig E, Lagarde J, Lai E, Leng J, Lu Z, MacCoss M, May G, McWhirter R, Merrihew G, Miller DM, Mortazavi A, Murad R, Oliver B, Olson S, Park PJ, Pazin MJ, Perrimon N, Pervouchine D, Reinke V, Reymond A, Robinson G, Samsonova A, Saunders GI, Schlesinger F, Sethi A, Slack FJ, Spencer WC, Stoiber MH, Strasbourger P, Tanzer A, Thompson OA, Wan KH, Wang G, Wang H, Watkins KL, Wen J, Wen K, Xue C, Yang L, Yip K, Zaleski C, Zhang Y, Zheng H, Brenner SE**, Graveley BR**, Celniker SE**, Gingeras TR**, Waterston R**.
Comparative analysis of the transcriptome across distant species. Nature 2014;512(7515):445-8.
Abstract
The transcriptome is the readout of the genome. Identifying common features in it across distant species can reveal fundamental principles. To this end, the ENCODE and modENCODE consortia have generated large amounts of matched RNA-sequencing data for human, worm and fly. Uniform processing and comprehensive annotation of these data allow comparison across metazoan phyla, extending beyond earlier within-phylum transcriptome comparisons and revealing ancient, conserved features. Specifically, we discover co-expression modules shared across animals, many of which are enriched in developmental genes. Moreover, we use expression patterns to align the stages in worm and fly development and find a novel pairing between worm embryo and fly pupae, in addition to the embryo-to-embryo and larvae-to-larvae pairings. Furthermore, we find that the extent of non-canonical, non-coding transcription is similar in each organism, per base pair. Finally, we find in all three organisms that the gene-expression levels, both coding and non-coding, can be quantitatively predicted from chromatin features at the promoter using a 'universal model' based on a single set of organism-independent parameters.
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