Lacra Bintu, PhD
Assistant Professor of Bioengineering
Department of Bioengineering
Stanford University

Department of Genetics

The sequence determinants of human transcriptional activators and repressors: high-throughput discovery and systematic perturbations

Hosted by:  Dr. Barak Cohen
In-person only:  Connor Auditorium (FLTC)

Talk abstract:  Human transcription factors (TFs) contain binding domains that allow them to recognize specific DNA sequences and effector domains that interact with transcriptional machinery or other cofactors to activate or repress transcription.

By performing high-throughput pooled measurements testing ~110,000 candidate sequences that are consecutive fragments from human transcription factors and chromatin regulators, we were able to pinpoint the exact location and strength of ~300 new activation and ~600 new repressive domains. By testing mutants of all these domains, we discovered that the sequences necessary for activation consist of hydrophobic amino acids interspersed with either acidic residues, prolines, glutamines or serines. In addition, we provided the first comprehensive categorization of repression domains based on the sequence necessary for function, and discovered that SUMOylation motifs are essential for repression in hundreds of TF domains. In addition we discovered a new class of effector domains that can both activate and repress, and can dynamically switch between these functions. Together, these results establish a compendium of human transcriptional effector domains and their sequence determinants, accelerating research across diverse areas, including gene regulation, developmental biology, immunology, and systems and synthetic biology.