Sarah C.R. Elgin, Ph.D.
Professor
Biology
Biochemistry and Molecular Biophysics
Education
Genetics
Molecular Genetics and Genomics Program
Developmental Biology Program
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Office Phone: 314-935-5348
Lab Phone: 314-935-6837
Other Phone:
FAX: 314-935-4432
Box: 1137
Lab Address: 131 McDonnell Hall
Email: selgin@biology.wustl.edu
Website: http://www.biology.wustl.edu/faculty/elgin.html
Keywords: gene expression; functional genomics; heterochromatin; RNAi; histone modification
Short Research Description: Chromatin structure and the control of gene expression in Drosophila. |
Research Abstract:
We are interested in the role that chromatin structure plays in gene regulation, both effects from packaging large domains and local effects of the nucleosome array. Working with Drosophila melanogaster, we have used a transposable P element containing a copy of the white gene, a visible marker for gene silencing, and a copy of hsp26, a well-characterized inducible gene, to examine the effect of insertion into different chromosomal domains. While these genes are fully active in euchromatic domains, silencing (similar to Position Effect Variegation) is observed on insertion into pericentric heterochromatin, telomeres, and sites within the small fourth chromosome. Both changes in the local nucleosome array, and the spatial organization of the nucleus, appear critical in determining gene silencing. While many P element insertion sites on the fourth chromosome induce silencing, others allow full expression; these sites are interspersed, indicating closely interspersed heterochromatic and euchromatic domains. We are characterizing these domains and their impact on gene expression. Mapping experiments indicate that heterochromatin formation is targeted by the presence of a repetitious element, 1360, and perhaps by other similar elements. Genetic analysis has shown that heterochromatic silencing is dependent on the RNAi machinery. Work is ongoing to determine the mechanism of heterochromatin targeting, and to analyze the role of critical heterochromatin-associated proteins, including HP1 and HP2. |
Selected Publications:
Brower-Toland B, Riddle NC, Jiang H, Huisinga KL and Elgin SCR. Multiple SET methyltransferases are required to maintain normal heterochromatin domains in the genome of Drosophila melanogaster. Genetics 2009 181: 1303-19.
Brower-Toland B, Findley SD, Jiang L, Liu L, Yin H, Dus M, Zhou P, Elgin SCR, and Lin H. Drosophila PIWI associates with chromatin and interacts directly with HP1a. Genes & Develop 2007 21:2300-2311.
Haynes KA, Caudy AA, Collins L, and Elgin SCR. Element 1360 and components of the RNAi system contribute to HP1-dependent silencing of a pericentric reporter. Current Biol 2006 16:2222-2227.
Shaffer C, Cenci G, Thompson B, Stephens GE, Slawson E, Adu-Wusu K, Gatti M, and Elgin SCR. The largo isoform of Drosophila melanogaster Heterochromatin Protein 2 plays a critical role in gene silencing and chromosome structure. Genetics 2006 174:1189-1204.
Sun FL, Haynes K, Simpson CL, et al. cis -Acting determinants of heterochromatin formation on Drosophila melanogaster chromosome four. Mol Cell Bio 2004: 8210-8220. |