Person:
Srinivasan, Sharanya

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Srinivasan

First Name

Sharanya

Name

Srinivasan, Sharanya

Filters

20171

Settings

Author's Publications: search.filters.isAuthorOfPublication.3ab062bd-b789-4022-aeab-47aab01b984f

Search Results

Now showing 1 - 1 of 1
  • No Thumbnail Available
    Publication
    High-Throughput Mapping of Diverse Functional Genomic Elements Governing BRCA2 Expression
    (2017-04-07) Srinivasan, Sharanya; Sherwood, Richard; Denkin, Steven
    The goal of this work is to develop a high-throughput approach to quantify the functional impact of the regulatory genome on target gene expression, and apply this system to catalogue functional cis-regulatory elements (CREs) that drive expression of BRCA2, a mutational driver of breast and ovarian cancer progression. The interactions between transcription factors and regulatory DNA modules underlie transcriptional outputs, but current techniques of cis-regulatory characterization utilize correlative features of enhancers, such as chromatin state, to assume CRE activity and do not measure the contributory effects of each CRE to a given target gene. Here we develop a CRISPR/Cas-based high-throughput screen to comprehensively and directly identify cis-regulatory sites that are necessary for BRCA2 expression by intercalating mutations across 185 kilobases of genomic space and using a fluorescence reporter to obtain measurements of diminished BRCA2 expression levels. We spatially map the distribution of required cis-regulatory sequences, and find evidence that proximal and distal elements exert controlling influences on BRCA2 expression. Multiple statistical evaluations of individual site and regional significance enable clarification of a diversified and spatially dispersed functional regulatory architecture governing BRCA2 transcription.