Histone Methylation Dynamics and Gene Regulation Occur through the Sensing of One-Carbon Metabolism.

Journal Article (Journal Article)

S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) link one-carbon metabolism to methylation status. However, it is unknown whether regulation of SAM and SAH by nutrient availability can be directly sensed to alter the kinetics of key histone methylation marks. We provide evidence that the status of methionine metabolism is sufficient to determine levels of histone methylation by modulating SAM and SAH. This dynamic interaction led to rapid changes in H3K4me3, altered gene transcription, provided feedback regulation to one-carbon metabolism, and could be fully recovered upon restoration of methionine. Modulation of methionine in diet led to changes in metabolism and histone methylation in the liver. In humans, methionine variability in fasting serum was commensurate with concentrations needed for these dynamics and could be partly explained by diet. Together these findings demonstrate that flux through methionine metabolism and the sensing of methionine availability may allow direct communication to the chromatin state in cells.

Full Text

Duke Authors

Cited Authors

  • Mentch, SJ; Mehrmohamadi, M; Huang, L; Liu, X; Gupta, D; Mattocks, D; Gómez Padilla, P; Ables, G; Bamman, MM; Thalacker-Mercer, AE; Nichenametla, SN; Locasale, JW

Published Date

  • November 3, 2015

Published In

Volume / Issue

  • 22 / 5

Start / End Page

  • 861 - 873

PubMed ID

  • 26411344

Pubmed Central ID

  • PMC4635069

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2015.08.024


  • eng

Conference Location

  • United States