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1.  Comparative analysis of metazoan chromatin organization 
Ho, Joshua W. K. | Jung, Youngsook L. | Liu, Tao | Alver, Burak H. | Lee, Soohyun | Ikegami, Kohta | Sohn, Kyung-Ah | Minoda, Aki | Tolstorukov, Michael Y. | Appert, Alex | Parker, Stephen C. J. | Gu, Tingting | Kundaje, Anshul | Riddle, Nicole C. | Bishop, Eric | Egelhofer, Thea A. | Hu, Sheng’en Shawn | Alekseyenko, Artyom A. | Rechtsteiner, Andreas | Asker, Dalal | Belsky, Jason A. | Bowman, Sarah K. | Chen, Q. Brent | Chen, Ron A-J | Day, Daniel S. | Dong, Yan | Dose, Andrea C. | Duan, Xikun | Epstein, Charles B. | Ercan, Sevinc | Feingold, Elise A. | Ferrari, Francesco | Garrigues, Jacob M. | Gehlenborg, Nils | Good, Peter J. | Haseley, Psalm | He, Daniel | Herrmann, Moritz | Hoffman, Michael M. | Jeffers, Tess E. | Kharchenko, Peter V. | Kolasinska-Zwierz, Paulina | Kotwaliwale, Chitra V. | Kumar, Nischay | Langley, Sasha A. | Larschan, Erica N. | Latorre, Isabel | Libbrecht, Maxwell W. | Lin, Xueqiu | Park, Richard | Pazin, Michael J. | Pham, Hoang N. | Plachetka, Annette | Qin, Bo | Schwartz, Yuri B. | Shoresh, Noam | Stempor, Przemyslaw | Vielle, Anne | Wang, Chengyang | Whittle, Christina M. | Xue, Huiling | Kingston, Robert E. | Kim, Ju Han | Bernstein, Bradley E. | Dernburg, Abby F. | Pirrotta, Vincenzo | Kuroda, Mitzi I. | Noble, William S. | Tullius, Thomas D. | Kellis, Manolis | MacAlpine, David M. | Strome, Susan | Elgin, Sarah C. R. | Liu, Xiaole Shirley | Lieb, Jason D. | Ahringer, Julie | Karpen, Gary H. | Park, Peter J.
Nature  2014;512(7515):449-452.
doi:10.1038/nature13415
PMCID: PMC4227084  PMID: 25164756
2.  Integrative Analysis of the Caenorhabditis elegans Genome by the modENCODE Project 
Gerstein, Mark B. | Lu, Zhi John | Van Nostrand, Eric L. | Cheng, Chao | Arshinoff, Bradley I. | Liu, Tao | Yip, Kevin Y. | Robilotto, Rebecca | Rechtsteiner, Andreas | Ikegami, Kohta | Alves, Pedro | Chateigner, Aurelien | Perry, Marc | Morris, Mitzi | Auerbach, Raymond K. | Feng, Xin | Leng, Jing | Vielle, Anne | Niu, Wei | Rhrissorrakrai, Kahn | Agarwal, Ashish | Alexander, Roger P. | Barber, Galt | Brdlik, Cathleen M. | Brennan, Jennifer | Brouillet, Jeremy Jean | Carr, Adrian | Cheung, Ming-Sin | Clawson, Hiram | Contrino, Sergio | Dannenberg, Luke O. | Dernburg, Abby F. | Desai, Arshad | Dick, Lindsay | Dosé, Andréa C. | Du, Jiang | Egelhofer, Thea | Ercan, Sevinc | Euskirchen, Ghia | Ewing, Brent | Feingold, Elise A. | Gassmann, Reto | Good, Peter J. | Green, Phil | Gullier, Francois | Gutwein, Michelle | Guyer, Mark S. | Habegger, Lukas | Han, Ting | Henikoff, Jorja G. | Henz, Stefan R. | Hinrichs, Angie | Holster, Heather | Hyman, Tony | Iniguez, A. Leo | Janette, Judith | Jensen, Morten | Kato, Masaomi | Kent, W. James | Kephart, Ellen | Khivansara, Vishal | Khurana, Ekta | Kim, John K. | Kolasinska-Zwierz, Paulina | Lai, Eric C. | Latorre, Isabel | Leahey, Amber | Lewis, Suzanna | Lloyd, Paul | Lochovsky, Lucas | Lowdon, Rebecca F. | Lubling, Yaniv | Lyne, Rachel | MacCoss, Michael | Mackowiak, Sebastian D. | Mangone, Marco | McKay, Sheldon | Mecenas, Desirea | Merrihew, Gennifer | Miller, David M. | Muroyama, Andrew | Murray, John I. | Ooi, Siew-Loon | Pham, Hoang | Phippen, Taryn | Preston, Elicia A. | Rajewsky, Nikolaus | Rätsch, Gunnar | Rosenbaum, Heidi | Rozowsky, Joel | Rutherford, Kim | Ruzanov, Peter | Sarov, Mihail | Sasidharan, Rajkumar | Sboner, Andrea | Scheid, Paul | Segal, Eran | Shin, Hyunjin | Shou, Chong | Slack, Frank J. | Slightam, Cindie | Smith, Richard | Spencer, William C. | Stinson, E. O. | Taing, Scott | Takasaki, Teruaki | Vafeados, Dionne | Voronina, Ksenia | Wang, Guilin | Washington, Nicole L. | Whittle, Christina M. | Wu, Beijing | Yan, Koon-Kiu | Zeller, Georg | Zha, Zheng | Zhong, Mei | Zhou, Xingliang | Ahringer, Julie | Strome, Susan | Gunsalus, Kristin C. | Micklem, Gos | Liu, X. Shirley | Reinke, Valerie | Kim, Stuart K. | Hillier, LaDeana W. | Henikoff, Steven | Piano, Fabio | Snyder, Michael | Stein, Lincoln | Lieb, Jason D. | Waterston, Robert H.
Science (New York, N.Y.)  2010;330(6012):1775-1787.
We systematically generated large-scale data sets to improve genome annotation for the nematode Caenorhabditis elegans, a key model organism. These data sets include transcriptome profiling across a developmental time course, genome-wide identification of transcription factor–binding sites, and maps of chromatin organization. From this, we created more complete and accurate gene models, including alternative splice forms and candidate noncoding RNAs. We constructed hierarchical networks of transcription factor–binding and microRNA interactions and discovered chromosomal locations bound by an unusually large number of transcription factors. Different patterns of chromatin composition and histone modification were revealed between chromosome arms and centers, with similarly prominent differences between autosomes and the X chromosome. Integrating data types, we built statistical models relating chromatin, transcription factor binding, and gene expression. Overall, our analyses ascribed putative functions to most of the conserved genome.
doi:10.1126/science.1196914
PMCID: PMC3142569  PMID: 21177976
4.  The Genomic Distribution and Function of Histone Variant HTZ-1 during C. elegans Embryogenesis 
PLoS Genetics  2008;4(9):e1000187.
In all eukaryotes, histone variants are incorporated into a subset of nucleosomes to create functionally specialized regions of chromatin. One such variant, H2A.Z, replaces histone H2A and is required for development and viability in all animals tested to date. However, the function of H2A.Z in development remains unclear. Here, we use ChIP-chip, genetic mutation, RNAi, and immunofluorescence microscopy to interrogate the function of H2A.Z (HTZ-1) during embryogenesis in Caenorhabditis elegans, a key model of metazoan development. We find that HTZ-1 is expressed in every cell of the developing embryo and is essential for normal development. The sites of HTZ-1 incorporation during embryogenesis reveal a genome wrought by developmental processes. HTZ-1 is incorporated upstream of 23% of C. elegans genes. While these genes tend to be required for development and occupied by RNA polymerase II, HTZ-1 incorporation does not specify a stereotypic transcription program. The data also provide evidence for unexpectedly widespread independent regulation of genes within operons during development; in 37% of operons, HTZ-1 is incorporated upstream of internally encoded genes. Fewer sites of HTZ-1 incorporation occur on the X chromosome relative to autosomes, which our data suggest is due to a paucity of developmentally important genes on X, rather than a direct function for HTZ-1 in dosage compensation. Our experiments indicate that HTZ-1 functions in establishing or maintaining an essential chromatin state at promoters regulated dynamically during C. elegans embryogenesis.
Author Summary
To fit within a cell's nucleus, DNA is wrapped around protein spools composed of the histones H3, H4, H2A, and H2B. One spool and the DNA wrapped around it are called a nucleosome, and all of the packaged DNA in a cell's nucleus is collectively called “chromatin.” Chromatin is important because it modulates access to information encoded in the underlying DNA. Spools with specialized functions can be created by replacing a typical histone component with a variant version of the histone protein. Here, we examine the distribution and function of the C. elegans histone H2A variant H2A.Z (called HTZ-1) during development. We demonstrate that HTZ-1 is required for proper development, and that embryos are dependent on a contribution of HTZ-1 from their mothers for survival. We mapped the location of HTZ-1 incorporation genome-wide and found that HTZ-1 binds upstream of 23% of genes, which tend to be genes that are essential for development and occupied by RNA polymerase. Fewer sites of HTZ-1 incorporation were found on the X chromosome, probably due to an under-representation of essential genes on X rather than a direct role for HTZ-1 in X-chromosome dosage compensation. Our study reveals how the genome is remodeled by HTZ-1 to allow the proper regulation of genes critical for development.
doi:10.1371/journal.pgen.1000187
PMCID: PMC2522285  PMID: 18787694

Results 1-4 (4)