Early-onset aging and mitochondrial defects associated with loss of histone acetyltransferase 1 (Hat1).

ABSTRACT: Histone acetyltransferase 1 (Hat1) is responsible for the acetylation of newly synthesized histone H4 on lysines 5 and 12 during the process of chromatin assembly. To understand the broader biological role of Hat1, we have generated a conditional mouse knockout model of this enzyme. We previously reported that Hat1 is required for viability and important for mammalian development and genome stability. In this study, we show that haploinsufficiency of Hat1 results in a significant decrease in lifespan. Defects observed in Hat1^+/- mice are consistent with an early-onset aging phenotype. These include lordokyphosis (hunchback), muscle atrophy, minor growth retardation, reduced subcutaneous fat, cancer, and paralysis. In addition, the expression of Hat1 is linked to the normal aging

SUBMITTER: Nagarajan P 

PROVIDER: S-EPMC6718594 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature