ATP-Citrate Lyase (ACL) interacts with histone acetyltransferase1 (HAT1) to stimulate histone H4K5 acetylation and cell cycle progression of developing endosperm in rice

Histone acetylation that marks open chromatin is dependent on histone acetyltransferases (HAT) that use acetyl-CoA to acetylate histone lysine residues. Fluctuation of cellular acetyl-CoA levels affects histone acetylation and gene expression. Acetyl-CoA used for histone acetylation is assumed to be mainly generated by ATP-citrate lyase (ACL) from glucose sources. Whether the ACL activity is linked to HAT function remains unclear. Here we showed that ACL physically interacts with distinct HATs to regulate histone acetylation at specific lysine residues. We showed that interaction between ACL and HAT1, previously shown to acetylate newly synthesized H4 in the cytoplasm in yeast and animal cells, is required for acetylation of nucleosomal histone H4K5 in rice. Mutations of rice ACL and HAT1 (HAG704) genes impaired cell division in developing endosperm and root meristem. CUT & Tag, RNA-seq and cytometry analysis of endosperm free nuclei revealed that both the acl and hag704 mutations decreased H4K5 acetylation at largely the same genomic regions, affected the expression of similar sets of genes that are enriched for starch metabolism and cell division functions, and resulted in S phase stagnation. ACL could stimulate HAT1 activity to specifically acetylate H4K5 in plant cells. Together, the results indicated that ACL directly interacts with distinct HATs to selectively regulate histone acetylation sites and revealed that ACL/HAT1-dependent nucleosomal H4K5 acetylation controls DNA replication and gene expression in rapidly dividing organs such as developing endosperm and root meristem which may play a role in integrating nutrition/energy levels to cell division decision.