BME 280B Seminar: Satellite repeats encode megabase-scale transcription factor hubs
Presenter: Matt Franklin, Postdoctoral Researcher, Stanford University
Description: Eukaryotic genomes contain large stretches of repetitive DNA called satellite DNA, often found near centromeres and ribosomal DNA regions. In humans, alpha satellite has well-established roles in centromere biology, however the functions of other human satellite DNAs remain largely unexplored.
We recently identified the Hippo pathway effector TEAD as a novel Human Satellite 3 (HSat3) binding TF. Because HSat3 is highly enriched near ribosomal DNA (rDNA) genes, we examined whether the Hippo pathway regulates rDNA via HSat3. Our work demonstrates that HSat3 localizes the Hippo factors YAP and TEAD inside the nucleolus, where YAP directly activates ribosomal RNA (rRNA) transcription. These findings present the first evidence that the Hippo pathway factor YAP directly regulates RNA Polymerase I activity.
Disparate studies have identified examples of transcription factors that bind repetitive DNA elements through motif recognition. However, a systematic search for such factors has not been conducted. Using Telomere-to-telomere genome assemblies, we predicted and validated dozens of new satellite-binding TFs, many of which are part of highly conserved signaling pathways. Beyond revealing a direct relationship between the Hippo pathway and ribosomal DNA regulation, this work demonstrates that satellite DNA can encode a broad range of functional motifs, hinting at new roles for these enormous genomic elements.
Bio: Following his undergraduate studies, Matt conducted a 1-year research fellowship at EMBL Hamburg, where he worked on X-ray scattering methods for structural biology. He then earned his PhD in chemical engineering at Stanford University, where he investigated mechanotransduction and Hippo pathway signaling. Matt continued this research as a postdoc under Kun-Liang Guan at UC San Diego, where he discovered that Hippo pathway effectors bind repetitive DNA elements. To expand on his newfound interest in repetitive DNA, Matt returned to Stanford as a postdoctoral researcher under Nicolas Altemose, where he is studying the functions of satellite repeats as hubs for transcription factor binding.
Hosted by: Professor Karen Miga, BME Department
