Both histone modification and chromatin-remodeling enzymes affect nucleosome dynamics in Saccharomyces cerevisiae
. Histone modification enzymes covalently modify various histones through chemical means, such as lysine acetylation, serine phosphorylation, lysine and arginine methylation, ubiquitylation, deimination, ADP ribosylation, and proline isomerization (18
). Chromatin-remodeling enzymes use the energy of ATP hydrolysis to induce nucleosome mobility or disrupt histone-DNA interactions (38
). NuA4 is a histone acetyltransferase complex responsible for global histone H4 acetylation (1
). The catalytic subunit of NuA4 is Esa1, which associates with Yng2p and Epl1p to form a smaller complex in vivo
named Piccolo NuA4 (8
). Piccolo NuA4 has a nontargeted histone acetyltransferase activity (8
), while the full NuA4 complex, united by the Eaf1 protein, carries out site-specific and targeted acetylation reactions (2
). The SWR1 complex (SWR1-C) is an ATP-dependent chromatin-remodeling complex that catalyzes the exchange of H2A-H2B with H2A.Z-H2B (H2A.Z is also known as Htz1) (17
). Notably, the platform proteins Eaf1 and Swr1 in NuA4 and SWR1-C, respectively, not only exhibit considerable sequence similarity to each other but also display strong and distinct homologies to human p400/Domino (2
), suggesting an evolutionary merging of functions in higher eukaryotes.
Heterochromatin was originally defined cytologically as genome blocks where the structure of chromatin is highly condensed throughout the cell cycle and hence remains transcriptionally silenced (36
). The main structural proteins of silent chromatin in S. cerevisiae
are known as silent information regulator (Sir) proteins and include Sir2, Sir3, and Sir4. The Sir complex propagates along chromatin to form an ordered and compact structure that is usually restrictive to transcription (35
Heterochromatin spreading is limited by boundary elements between silenced and active chromatin (35
). These barriers appear to fall into two classes (6
). The first class of barrier confers a structural characteristic to the boundary region, such as gaps in nucleosomes or association with nuclear pores. The second class of barrier is more dynamic and involves modification of heterochromatin-proximal regions in a wide area. Local chromatin dynamics can counteract the repressive Sir activity and prevent further spread of silencing.
Both SWR1-C and NuA4 have been linked to antisilencing functions at heterochromatin boundaries (11
), however, their functional interplay in antisilencing is not yet clear. In this study, we dissected the individual and coupled actions of SWR1-C and NuA4 at antisilencing regions. By studying the functions of Swc4, we discovered an intrinsic relationship between NuA4 and SWR1-C in the establishment of a chromatin boundary.