General Biology Seminar

Friday, February 21, 2014

4:00pm to 5:00pm

Kerckhoff 119

Interrogating gene regulatory circuit function using natural variation in animals

Zeba Wunderlich, Postdoctoral Fellow, Biophysics, Harvard Medical School,

Abstract: The long-term goal of my work is to understand how regulatory information is encoded

in animal genomes using high-resolution imaging, genetics, computational models and

bioinformatics. Regulatory DNA, e.g. enhancers, can be thought of as the "wiring diagram" for a

transcriptional circuit, whose output is gene expression and whose inputs are regulatory

molecules like transcription factors (TFs). Because enhancers change rapidly in sequence over

even short evolutionary time, examining the expression patterns driven orthologous enhancers

can elucidate the rules governing the sequence-function relationship of enhancers. However,

multiple components of transcriptional circuits change during evolution, so changes in gene

expression output can be caused by either changes in the circuit's inputs or changes in the

circuit wiring. Even when an expression pattern is conserved between species,

the regulatory DNA and TFs can be functionally divergent, yet work together to produce a

similar expression pattern of their target gene. Therefore, to understand sequence-function

relationships of regulatory DNA, we must first control for gene expression divergence due to

changing inputs.

Using transcriptional circuits in the anterior-posterior patterning network in Drosophila

blastoderm stage embryos, we have developed a modeling framework for disentangling the

contributions of changes in enhancers and changes in the expression pattern of their TF inputs.

Using cellular-resolution imaging techniques, we created atlases of gene expression for key TFs

in the anterior-posterior patterning

network in several Drosophila species. We use these data and modeling framework to compare

the function of two transcriptional circuits in the embryo that show differing patterns of

conservation. We expect to generalize this approach to other types of regulatory DNA and

transcriptional circuits in other systems to understand how sequence divergence affects

regulatory function and its implications for the

evolution of gene regulation.

For more information, please contact Joanne Meraz by phone at x 4953 or by email at [email protected].

Event Series

General Biology Seminar Series

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