If modules are defined as densely interconnected networks with sparse external connections, it follows that interaction between modules is limited -- a property referred to as 'insulation'. But there are biological systems, such as the yeast Environmental Stress Response (ESR), in which stimulation of distinct signaling pathways leads to both signal-specific outcomes and others that are generic -- that is, common to many different signals. Systems such as the ESR raise the question of how signaling pathways can interact at common promoters without activating inappropriate stimulus-specific promoters. In other words, how are modules connected to a common response while otherwise remaining insulated from each other? In the case of the ESR, induction in response to different stresses depends on different transcription factors, demonstrating that the convergence of these signaling pathways does not occur upstream of a common transcription factor. Thus, these genes act as 'OR' gates for a number of signaling pathways, pointing to chromatin structure as one of the few possible remaining steps at which signal integration may occur. We are developing techniques for the high-resolution study of chromatin structure, to use in the study of promoters of ESR genes. We will examine the chromatin structure and histone modification state of these promoters upon induction by a variety of stresses. Data from these studies will be analyzed to attempt to discern general rules for the effects of chromatin environment on gene expression. In addition to adding to the understanding of connections between modules, a greater understanding of chromatin's influence on gene expression will be of great clinical benefit, as it is becoming increasingly clear that misregulation of chromatin structure and modification state is central to a number of important disease processes, including a number of types of cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM068763-02
Application #
7557299
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$147,864
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Westerman, Erica L; VanKuren, Nicholas W; Massardo, Darli et al. (2018) Aristaless Controls Butterfly Wing Color Variation Used in Mimicry and Mate Choice. Curr Biol 28:3469-3474.e4
Bonham, Kevin S; Wolfe, Benjamin E; Dutton, Rachel J (2017) Extensive horizontal gene transfer in cheese-associated bacteria. Elife 6:
Lavrentovich, Maxim O; Wahl, Mary E; Nelson, David R et al. (2016) Spatially Constrained Growth Enhances Conversional Meltdown. Biophys J 110:2800-2808
Battle, Christopher; Broedersz, Chase P; Fakhri, Nikta et al. (2016) Broken detailed balance at mesoscopic scales in active biological systems. Science 352:604-7
Tamari, Zvi; Yona, Avihu H; Pilpel, Yitzhak et al. (2016) Rapid evolutionary adaptation to growth on an 'unfamiliar' carbon source. BMC Genomics 17:674
Kim, Wook; Levy, Stuart B; Foster, Kevin R (2016) Rapid radiation in bacteria leads to a division of labour. Nat Commun 7:10508
Muller, Nicolas; Piel, Matthieu; Calvez, Vincent et al. (2016) A Predictive Model for Yeast Cell Polarization in Pheromone Gradients. PLoS Comput Biol 12:e1004795
Wahl, Mary E; Murray, Andrew W (2016) Multicellularity makes somatic differentiation evolutionarily stable. Proc Natl Acad Sci U S A 113:8362-7
Hormoz, Sahand; Singer, Zakary S; Linton, James M et al. (2016) Inferring Cell-State Transition Dynamics from Lineage Trees and Endpoint Single-Cell Measurements. Cell Syst 3:419-433.e8
Renn, Suzy C P; O'Rourke, Cynthia F; Aubin-Horth, Nadia et al. (2016) Dissecting the Transcriptional Patterns of Social Dominance across Teleosts. Integr Comp Biol 56:1250-1265

Showing the most recent 10 out of 205 publications