Dale Dorsett, Ph.D.
Chromosome structure control of gene expression during development using Drosophila molecular genetics and elucidation of the molecular mechanisms of Cornelia de Lange syndrome.
Office: DRC, Room 423
Phone: (314) 977-9218
Ph.D., 1980, University of Tennessee Oakridge National Laboratory
We use Drosophila molecular genetics to understand how chromosome structure controls gene expression during development. Our studies have shed light on the molecular mechanisms of Cornelia de Lange syndrome, which causes diverse developmental deficits in humans.
- Cornelia de Lange syndrome and molecular implications of the cohesin complex: Abstracts from the 7th biennial scientific and educational symposium 2016.
Kline AD, Krantz ID, Deardorff MA, Shirahige K, Dorsett D, Gerton JL, Wu M, Mehta D, Mills JA, Carrico CS, Noon S, Herrera PS, Horsfield JA, Bettale C, Morgan J, Huisman SA, Moss J, McCleery J, Grados M, Hansen BD, Srivastava S, Taylor-Snell E, Kerr LM, Katz O, Calof AL, Musio A, Egense A, Haaland RE. Am J Med Genet A. (2017) Feb 12 [Eppub ahead of print].
- Measuring sister chromatid cohesion protein genome occupancy in Drosophila melanogaster by ChIP-seq.
Dorsett D, Misulovin Z. Methods Mol Biol. (2017) 1515:125-139.
- Drosophila TDP-43 RNA-binding protein facilitates association of sister chromatid cohesion proteins with genes, enhancers and polycomb response elements.
Swain A, Misulovin Z, Pherson M, Gause M, Mihindukulasuriya K, Rickels RA, Shilatifard A, Dorsett D. PLoS Genet. (2016) 12(9):e1006331.
- Vitamin D receptor signaling improves Hutchinson-Gilford progeria syndrome cellular phenotypes.
Kreienkamp R, Croke M, Neumann MA, Bedia-Diaz G, Graziano S, Dusso A, Dorsett D, Carlberg C, Gonzalo S. Oncotarget. (2016) 7(21):30018-30031.
- The Drosophila melanogaster model for Cornelia de Lange syndrome: Implications for etiology and therapeutics.
Dorsett D. Am J Med Genet C Semin Med Genet. (2016) 172(2):129-137.
Chip, a widely expressed chromosomal protein required for segmentation and activity of a remote wing margin enhancer in Drosophila.
Patrick Morcillo, Christina Rosen, Mary K. Baylies, and Dale Dorsett.
Genes Dev. 11(20):2729-2740, 1997. (PMID 9334334)
This paper describes the cloning and functional characterization of the Chip/Ldb1 gene that is essential for the activity of many diverse transcriptional enhancers. Although our laboratory no longer actively works on this gene and protein, this paper stimulated several other laboratories to study its functions in diverse developmental and differentiation processes, including hematopoiesis, neurological development, and leukemia.
Model for regulation of cut by the remote wing margin enhancer and the sd, mam, and Chip genes.
Nipped-B, a Drosophila homologue of chromosomal adherins, participates in activation by remote enhancers in the cut and Ultrabithorax genes.
Robert A. Rollins, Patrick Morcillo and Dale Dorsett.
Genetics. 152(2):577-593, 1999. (PMID 10353901)
This paper described the genetic discovery, cloning and characterization of the Nipped-B gene that supports both sister chromatid cohesion and unexpectedly, the mechanisms that support long-range gene activation. This has turned out to be important in development, human genetic diseases, and cancer. It forms the basis of most of our laboratories current work, and the functions of this gene and protein are now intensively studied by dozens of laboratories around the world.
Dominant enhancement of the ct53d partial cut cause bithorax phenotypes in combination with heterowing phenotype by some Nipped mutations.
Association of cohesin and Nipped-B with transcriptionally active regions of the Drosophila melanogaster genome.
Ziva Misulovin, Yuri B. Schwartz, Xiao-Yong Li, Tatyana G. Kahn, Maria Gause, Stewart MacArthur, Justin C. Fay, Michael B. Eisen, Vincenzo Pirrotta, Mark D. Biggin, and Dale Dorsett.
Chromosoma. 117(1):89-102, 2008. (PMID 17965872)
This paper reports the first genome-wide analysis of the chromosome binding of the Nipped-B protein and cohesin complex essential for sister chromatid cohesion and chromosome segregation in a metazoan organism. The key finding is that these proteins only bind to genes when they are actively transcribed, and primarily to a subset of genes that are critical for growth and development. These findings form the basis of our current efforts to determine the mechanisms by which these proteins facilitate regulation of transcription and development. We reported multiple mechanisms that we have discovered, including support of enhancer-promoter communication and control of gene silencing, in subsequent papers.
Binding of Nipped-B, cohesin subunits, and PolII to a 2 Mb region of chromosome 3L. This region was chosen to illustrate typical features of cohesin and Nipped-B binding patterns seen throughout the genome.