title: Serine and SAM Responsive Complex SESAME Regulates Histone Modification Crosstalk by Sensing Cellular Metabolism.
abstract: Pyruvate kinase M2 (PKM2) is a key enzyme for glycolysis and catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate, which supplies cellular energy. PKM2 also phosphorylates histone H3 threonine 11 (H3T11); however, it is largely unknown how PKM2 links cellular metabolism to chromatin regulation. Here, we show that the yeast PKM2 homolog, Pyk1, is a part of a novel protein complex named SESAME (Serine-responsive SAM-containing Metabolic Enzyme complex), which contains serine metabolic enzymes, SAM (S-adenosylmethionine) synthetases, and an acetyl-CoA synthetase. SESAME interacts with the Set1 H3K4 methyltransferase complex, which requires SAM synthesized from SESAME, and recruits SESAME to target genes, resulting in phosphorylation of H3T11. SESAME regulates the crosstalk between H3K4 methylation and H3T11 phosphorylation by sensing glycolysis and glucose-derived serine metabolism. This leads to auto-regulation of PYK1 expression. Thus, our study provides insights into the mechanism of regulating gene expression, responding to cellular metabolism via chromatin modifications.
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Li
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Madelaine
authors.initials: M
authors.lastname: Gogol
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA; Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50(th) Street, Kansas City, MO 64110, USA. Electronic address: tas@stowers.org.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Suganuma
mesh_terms: D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D015966:Gene Expression Regulation, Fungal / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D011505:Protein-Tyrosine Kinases