Sarah C.R. Elgin, Ph.D.

Professor
Biology
Genetics
Education

Molecular Genetics and Genomics Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-935-5348

  • 314-935-6837

  • 314-935-4432

  • 1137

  • 131 McDonnell Hall

  • selgin@biology.wustl.edu

  • http://www.biology.wustl.edu/faculty/elgin/

  • gene expression, functional genomics, heterochromatin, RNAi, histone modification

  • 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. As part of the modENCODE consortium we have mapped the distribution of histone modifications and prominent chromosomal proteins across the genome as a whole. The distal 1.2 Mb of the fourth chromosome is distinct in having both a high gene density and a high density of heterochromatin marks, including HP1a (Heterochromatin Protein 1) and histone H3K9me2/3. How these genes function is under investigation. Mapping experiments indicate that heterochromatin formation is targeted by the presence of a transposable element (TE) remnant, 1360, and by other similar elements. Genetic analysis has shown that heterochromatic silencing of our reporters is dependent on the RNAi machinery; we find that Piwi (the piRNA binding protein) is critical for HP1a deposition at some Tes. Piwi appears to play a role in setting up heterochromatin structure in the early embryo, but is not required to maintain silencing in the eye linage. Work is ongoing to determine the mechanism of heterochromatin targeting, and to analyze the role of critical heterochromatin-associated proteins.

Selected Publications:

Gu, T, and Elgin, SCR (2013) Maternal delpletion of Piwi, a component of the RNAi system, impacts heterochromatin formation in Drosophila. PLoS Genetics 9: e1003780/ PMCID: PMC3777992

Sentmanat, M, and SCR Elgin. (2012) Ectopic assembly of heterochromatin in Drosophila triggered by transposable elements. Proc Natl Acad Sci USA 109: 14104- 9. PMCID: PMC3435190

Riddle, NC, YL Jung, T Gu, AA Alekseyenko, D Asker, H Gui, PV Kharchenko, A Minoda, A Plachetka, YB Schwartz, MY Tolstorukov, MI Kuroda, V Pirrotta, GH Karpen, PJ Park, SCR Elgin. (2012) “Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternative chromatin structure critical for regulation in this heterochromatic domain,” PLoS Genetics 8: e1002954

Wang SH and Elgin SCR. (2011). Drosophila Piwi functions downstream of piRNA production mediating a chromatin-based silencing mechanism in female germline. Proc Natl Acad Sci USA 108: 21164-69. PMCID: PMC3248523.

Kharchenko PV, Alekseyenko AA, Schwartz YB, Minoda A, Riddle NC, Ernst J, Sabo PJ, Larschan E, Gorchakov AA, Gu T, Linder-Basso D, Plachetka A, Shanower G, Tolstorukov MY, Luquette LJ, Xi R, Jung YL, Park R, Bishop EP, Canfield TP, Sandstrom R, Thurman RE, MacAlpine DM, Stamatoyannopoulos J, Kellis M, Elgin SCR, Kuroda MI, Pirrotta V, Karpen G, Park PJ. Comprehensive analysis of the chromatin landscape in Drosophila melanogaster. Nature 2011 471: 480-5. PMCID: PMC3109908

Riddle NC, Minoda A, Kharchenko PV, Alekseyenko AA, Schwartz YB, Tolstorukov MY, Gorchakov AA, Kennedy C, Linder-Basso D, Jaffe JD, Shanower G, Kuroda MI, Pirrotta V, Park PJ, Elgin SCR, Karpen GH. Plasticity in patterns of histone modifications and chromosomal proteins in the Drosophila heterochromatin. Genome Res. 2011 21:147-63. PMID: 21177972

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. 2009 Genetics 181: 1303-19. PMID: 19189944 PMCID: PMC2666501

Riddle NC, Leung W, Haynes KA, Granok H, Wuller J and Elgin SCR. An investigation of heterochromatin domains on the fourth chromosome of Drosophila melanogaster. Genetics 2008 178: 1177-1191. PMID: 18245350 PMCID: PMC2278077

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. PMID: 17113386 PMCID: PMC1712676

Last Updated: 8/11/2014 11:32:56 AM

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