HUH Seminar Series - Aman Husbands

Dr. Aman Husbands
Mitchell J. Blutt and Margo Krody Blutt Presidential Assistant Professor of Biology
University of Pennsylvania

Title: Distinct transcriptional outcomes from an overlapped genetic network architecture

Abstract: Functional divergence of transcription factors (TFs) has driven cellular and organismal complexity throughout evolution, but its mechanistic drivers remain poorly understood. Here we test for new mechanisms using CORONA (CNA) and PHABULOSA (PHB), two functionally diverged members of the CLASS III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIPIII) family of TFs. We show that virtually all genes bound by PHB (~99.5%) are also bound by CNA, ruling out occupation of distinct sets of genes as a mechanism of functional divergence. Further, genes bound and regulated by both paralogs are almost always regulated in the same direction, ruling out opposite regulation of shared targets as a mechanistic driver. Functional divergence of CNA and PHB instead results from differential usage of shared binding sites, with hundreds of uniquely regulated genes emerging from a commonly bound genetic network. Regulation of a given gene is thus a function of whether the binding sites in its regulatory region are considered primed (inactive/ unused) or regulated (active/used) by CNA or PHB. This decision is controlled, at least in part, by their lipid binding START domain, proposing a model in which HD-ZIPIII TFs use information integrated by their START domain to generate paralog-specific transcriptional outcomes at commonly bound genes. Taken together, our study identifies a new mechanism of TF paralog divergence and proposes the ubiquitously distributed START evolutionary module as a driver of functional divergence.

Hosted by: Kramer Lab

Join via livestream: https://harvard.zoom.us/meeting/register/tJwpdOitqDktE9cvPWDI91LEQ8GmVrGEpW_3 (registration required)