Arnosti Laboratory

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The Arnosti laboratory studies gene regulation in the context of development. A main focus of our laboratory’s research has been understanding the “cis regulatory grammar” by which combinations of transcription factor binding sites in regulatory regions provide precise outputs for genes regulated in tissue- and temporal-specific patterns. A second related area concerns transcriptional repressors and corepressors, which are key contributors to this regulation.  Our research has provided novel insights into biochemical and genetic pathways regulated by these factors. The powerful genetics and molecular biology of Drosophila allows us to test the importance of cis- and trans-acting regulators of transcription in a developmental setting. This fundamental research is critical for understanding the central regulatory mechanisms in biology, including in development, disease, and evolution.

Main concepts in gene regulation that have stemmed from our research include:

1. Transcriptional enhancers function as “billboards”, allowing a flexible display of regulatory potential from different surfaces of bound activators and repressors.

2. Long- and short-range repression mechanisms represent fundamentally different ways in which the cell deploys chromatin-modifying machinery to achieve either very tightly targeted, acute impacts on enhancers, or widespread blanket suppression of regulatory information.

3. Cis-regulatory grammar of binding sites can be revealed by deep perturbation analysis of enhancers in vivo, combined with mathematical (fractional occupancy) modeling to reveal potential biochemical parameters – in essence, a prediction of how transcription factors “feel about” binding in an enhancer, next to other factors.

4. Transcriptional repressors play key roles in generating patterned gene expression in development, but they also are critical modulators of widely expressed genes that do not show a complete on/off regulation. This “soft repression” represents an essential layer of regulatory control that has been poorly investigated, for historical and technical reasons.

Current Research

news

Kurtulus Kok receives Ph.D. May 15, 2015 Kurtulus Kok receives Ph.D.

May 2015: Kurtulus Kok successfully defends his Ph.D. research on genome-wide chromatin modifications by the Hairy repressor (see here with Sandhya Payankaulam, Yiliang Wei, David Arnosti and Rewatee Gokhale)

May 1, 2015 Special Symposium: evolution and core processes in gene regulation

When: June 25 - 28

Where: St. Louis, Mo

April 9, 2015 GSA Poster Awards for 56th Annual Drosophila Research Conference

BETHESDA, MD –The Genetics Society of America (GSA) and the Drosophila research community are pleased to announce the winners of the GSA poster awards at the 56th Annual Drosophila Research Conference, which took place in Chicago, IL, March 4–8, 2015. 

Annual Drosophila Research Conference March 9, 2015 Annual Drosophila Research Conference

Arnosti Laboratory at the Annual Drosophila Research Conference, Chicago IL March 2015.