The Largest Subunit of Human TFIIIC Complex, TFIIIC220, a Lysine Acetyltransferase Targets Histone H3K18

Abstract

TFIIIC is a multi-subunit complex required for tRNA transcription by RNA polymerase III. Human TFIIIC holo-complex possesses lysine acetyltransferase activity that aids in relieving chromatin-mediated repression for RNA polymerase III-mediated transcription and chromatin assembly. Here we have characterized the acetyltransferase activity of the largest and DNA-binding subunit of TFIIIC complex, TFIIIC220. Purified recombinant human TFIIIC220 acetylated core histones H3, H4 and H2A in vitro. Moreover, we have identified the putative catalytic domain of TFIIIC220 that efficiently acetylates core histones in vitro. Mutating critical residues of the putative acetyl-CoA binding 'P loop' drastically reduced the catalytic activity of the acetyltransferase domain. Further analysis showed that the knockdown of TFIIIC220 in mammalian cell lines dramatically reduces global H3K18 acetylation level, which was rescued by overexpression of the putative acetyltransferase domain of human TFIIIC220. Our findings indicated a possibility of a crucial role for TFIIIC220 in maintaining acetylation homeostasis in the cell.

Keywords: C646; H3K18ac; TFIIIC220; acetyltransferase; embelin.