Description:

The Department of Biochemistry and Molecular Genetics presents:

Yingming Zhao, Ben May Department of Cancer Research, The University of Chicago

Seminar Title: Lactate‐mediated Histone Lysine Lactylation: Chemistry, Proteome and Biochemistry

Abstract:

We and others have recently demonstrated a family of lysine acylation modifications, which can have a unique set of substrate proteins, “writers”, “erasers”, and “readers”. These pathways have regulatory roles in epigenetic mechanism and cellular metabolism program, and contribute to physiological changes and cellular dysfunctions associated with diseases. In this presentation, we will report our recent identification and characterization of a new type of epigenetic pathway, lysine lactylation (Kla). We comprehensively confirmed this modification using diverse chemical and immunochemical approaches. Histone Kla is very dynamic in response to elevated concentration of lactate and diverse cellular environments that can stimulate production of lactate. Using proteomics in combination with other chemical and biochemical tools, we identified substrates and regulatory elements (lactyltransfeases and delactylases) for this modification pathway. We used ChIP-seq and RNA-seq analysis to demonstrate that the histone Kla marks are associated with gene expression and have physiological relevance distinct from histone acetylation. These studies therefore reveal a new type of histone marks that is associated with dynamic changes of lactate, a metabolite closely linked to the Warburg effect and diverse pathophysiology, including hypoxia.