The study investigates the role of ATP-citrate lyase (ACL) in histone acetylation in mammalian cells. ACL is an enzyme that converts citrate into acetyl-CoA, which is crucial for histone acetylation. The research shows that ACL is essential for increasing histone acetylation in response to growth factor stimulation and during differentiation. Glucose availability also impacts histone acetylation, and this effect is ACL-dependent. The findings suggest that ACL activity links nutrient metabolism to histone acetylation and gene expression regulation. The study further demonstrates that ACL-dependent acetylation can influence the expression of genes involved in glucose metabolism, highlighting the dynamic regulation of histone acetylation by changes in acetyl-CoA production.The study investigates the role of ATP-citrate lyase (ACL) in histone acetylation in mammalian cells. ACL is an enzyme that converts citrate into acetyl-CoA, which is crucial for histone acetylation. The research shows that ACL is essential for increasing histone acetylation in response to growth factor stimulation and during differentiation. Glucose availability also impacts histone acetylation, and this effect is ACL-dependent. The findings suggest that ACL activity links nutrient metabolism to histone acetylation and gene expression regulation. The study further demonstrates that ACL-dependent acetylation can influence the expression of genes involved in glucose metabolism, highlighting the dynamic regulation of histone acetylation by changes in acetyl-CoA production.