Roles of CAF-1 in DNA replication-coupled assembly of euchromatin and heterochromatin. a During euchromatic DNA replication, PCNA is loaded at the fork. Newly synthesized histone H3–H4 dimers, acetylated by specific histone acetyltransferases (HATs), are brought by Asf1 to the nascent DNA site, then transferred onto the CAF-1 complex, forming a H3–H4 tetramer. Together with the H2A–H2B tetramer brought by Nap1, these acetylated H3–H4 tetramers are assembled into nucleosomes, which consist of mixed histones, either parental or newly synthesized. b During de novo heterochromatin formation, K9 residues on histone H3 tails are mono-methylated by SetDB1 of the CAF-1/HP-1/SetDB1 complex. SU(VAR)3–9 is responsible for the di- and tri-methylation of H3K9 (H3K9me2/3) based on mono-methylated H3K9 (H3k9me1)