The division of chromosomes into euchromatic and heterochromatic regions is an enigmatic aspect of genome organization in multicellular eukaryotes. Heterochromatin is a major component of genomes as diverse as humans and fruit flies, and plays critical roles in chromosome inheritance and metabolism. In the absence of a detailed analysis of heterochromatin organization and sequence, our ability to investigate chromosome function, heterochromatic genes, and genome evolution remains limited. In the previous granting period, the Drosophila Heterochromatin Genome Project (DHGP) used genomic resources available in Drosophila melanogaster to generate basic information about the structure and sequence composition of the heterochromatin, specifically focusing on gene- and transposable element- rich regions that do not contain long arrays of highly-repeated satellite DNAs. We have assembled 12.5Mb of finished or nearly finished sequence and a BAC-based physical map that spans 16.5Mb of the heterochromatin, and linked sequences and clones to specific locations in the cytological maps. Annotation of 49Mb of sequence identified 700 gene models and other genetic elements, as well as orthologs in other Drosophilids, and demonstrated that >85% of the target sequences contains repetitive DNA. Here, we propose to extend the D. melanogaster heterochromatin sequence and physical maps to encompass most or all of the non-satellite regions, and to initiate studies of satellite regions. We will also to improve annotations and public data displays, examine evolution of heterochromatin through comparative analysis with other Drosophila species, and develop tools to facilitate heterochromatin assemblies and analysis. Achieving these aims will provide information and tools that will further our understanding of higher eukaryotic genome structure, and will lay the groundwork for more complete analysis of heterochromatin structure and function in Drosophila and other eukaryotes, including humans. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG000747-16
Application #
7470728
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Felsenfeld, Adam
Project Start
1992-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2010-06-30
Support Year
16
Fiscal Year
2008
Total Cost
$1,172,711
Indirect Cost
Name
Lawrence Berkeley National Laboratory
Department
Genetics
Type
Organized Research Units
DUNS #
078576738
City
Berkeley
State
CA
Country
United States
Zip Code
94720
Hoskins, Roger A; Carlson, Joseph W; Wan, Kenneth H et al. (2015) The Release 6 reference sequence of the Drosophila melanogaster genome. Genome Res 25:445-58
Xia, Ai; Sharakhova, Maria V; Leman, Scotland C et al. (2010) Genome landscape and evolutionary plasticity of chromosomes in malaria mosquitoes. PLoS One 5:e10592
Hoang, Margaret L; Tan, Frederick J; Lai, David C et al. (2010) Competitive repair by naturally dispersed repetitive DNA during non-allelic homologous recombination. PLoS Genet 6:e1001228
Werren, John H; Richards, Stephen; Desjardins, Christopher A et al. (2010) Functional and evolutionary insights from the genomes of three parasitoid Nasonia species. Science 327:343-8
Sharakhova, Maria V; George, Phillip; Brusentsova, Irina V et al. (2010) Genome mapping and characterization of the Anopheles gambiae heterochromatin. BMC Genomics 11:459
Karpen, Gary H (2009) Preparation of high-molecular-weight DNA from Drosophila embryos. Cold Spring Harb Protoc 2009:pdb.prot5254
Peng, Jamy C; Karpen, Gary H (2008) Epigenetic regulation of heterochromatic DNA stability. Curr Opin Genet Dev 18:204-11
Smith, Christopher D; Edgar, Robert C; Yandell, Mark D et al. (2007) Improved repeat identification and masking in Dipterans. Gene 389:1-9
Hoskins, Roger A; Carlson, Joseph W; Kennedy, Cameron et al. (2007) Sequence finishing and mapping of Drosophila melanogaster heterochromatin. Science 316:1625-8
(2007) Evolution of genes and genomes on the Drosophila phylogeny. Nature 450:203-18

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