May
28
2024
Stealing the code: How SetDB1 regulates heterochromatin spreading
Katalin Fejes Tóth
California Institute of Technology
hosted by Karsten Rippe
4:00 PM SR41
Abstract
Heterochromatin plays an essential role in nuclear organization and regulation of gene expression by directing the 3D genome organization, regulating lineages-specific gene expression and ensuring repression of transposable elements and endogenous retroviruses. Functionally and structurally different chromatin domains are discriminated by the so-called histone code, combinations of post-translational modifications of histones that are deposited by code-writers and recognized by code-readers. The main mark of heterochromatin, trimethylation of histone H3 tail at lysine 9 (H3K9me3) is deposited by histone methyltransferases, such SetDB1, and provides a binding platform for readers, most significantly, HP1 family proteins. How heterochromatin spreads from nucleation sites to establish large repressive domains and how these domains are stably maintained is not fully understood. Using a reporter to monitor dynamics of heterochromatin establishment and maintenance, we show the existence of a feedback mechanism by which the reader of the H3K9me3 mark, HP1, attracts the writer, SetDB1 through direct physical interaction that depends on posttranslational modifications of SetDB1. These modifications of SetDB1 are required for the spreading and stable maintenance of heterochromatin
Biosketch
Katalin Fejes Tóth obtained her MD in 2001 from the Semmelweis Medial University in Budapest and her PhD in the field of biochemistry and biophysics from Heidelberg University in 2004. She performed her postdoctoral studies in the lab of Gregory Hannon at Cold Spring Harbor Laboratory (2006 – 2009). She established her independent research lab at the California Institute of Technology (Caltech) in the Division of Biology and Biological Engineering in 2010 with a general focus in the fields of transcriptional regulation, chromatin, RNA and developmental biology. Her lab studies the cellular and developmental functions and molecular mechanisms of regulation of selfish genetic elements.