Combinatorial gene regulation by transcription factors

Combinatorial gene regulation is encoded in enhancers and promoters in the form of binding sites for transcription factors (TFs), which collaboratively recruit the transcriptional machinery and drive gene expression. Using high-throughput and quantitative technologies developed by our lab and others, we studied TF binding sites in enhancers from numerous different cell types and regulatory systems, shedding light general principles of motif composition and organization in typical cellular regulatory elements. We find extensive synergy between TF binding sites, some with organizational constraints and some with flexible positioning. We demonstrate that different TFs bind at distinct positions within regulatory elements, suggesting a new type of architectural constraint in enhancers. Importantly, our analysis of both TF organization and cooperativity revealed distinctive patterns that separates TFs into potential functional classes. Together, our results suggest a structure of the regulatory code at the level of TF function and generate new hypotheses about regiospecific binding patterns and functions of TF classes within enhancers.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Grossman, Sharon R.(Sharon Rachel)

Advisor dc:contributor.advisor

• Eric S. Lander.

• Biology.

Statement dc:rights

• MIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/128406

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/128406