Hyperacetylated histone H4 is a source of carbon contributing to lipid synthesis

ABSTRACT: Histone modifications commonly integrate environmental cues with cellular metabolic outputs by affecting gene expression. However, chromatin modifications such as acetylation do not always correlate with transcription, pointing towards an alternative role of histone modifications in cellular metabolism. Using an approach that integrates mass spectrometry-based histone modification mapping and metabolomics with stable isotope tracers, we demonstrate that elevated lipids in acetyltransferase-depleted hepatocytes result from carbon atoms derived from deacetylation of hyperacetylated histone H4 flowing towards fatty acids. Consistently, enhanced lipid synthesis in acetyltransferase-depleted hepatocytes is dependent on histone deacetylases and acetyl-CoA synthetase ACSS2, but not on the substra

SUBMITTER: Dr. Evelina Charidemou 

PROVIDER: S-SCDT-10_1038-S44318-024-00053-0 | biostudies-other |

REPOSITORIES: biostudies-other