Loss of ATAC-specific acetylation of histone H4 at Lys12 reduces binding of JIL-1 to chromatin and phosphorylation of histone H3 at Ser10

Abstract

Various combinations of post-translational modifications of the N-terminal tails of nucleosomal histones serve as signals to govern chromatin-related processes. The relationship, however, among different types of histone modifications – most frequently acetylation, phosphorylation and methylation – and the order of their establishment has been explored only in a few cases. Here we show that a reduced level of histone H4 acetylated at Lys12 by the ATAC-HAT complex leads to a decrease in the histone H3 phosphorylation at Ser10 by the kinase JIL-1. As JIL-1 activity antagonizes histone H3 dimethylation at Lys9 by SU(VAR)3-9, our observations demonstrate the interdependent actions of an acetyltransferase, a kinase and a methyltransferase. We demonstrate that, in accord with the steps of modifications, mutations that affect ATAC subunits (such as dGcn5, dAda2a and dAda3) (1) decrease the level histone H3 phosphorylation at Ser10, (2) can be rescued partially by JIL-1 overproduction, (3) enhance the spread of histone H3 dimethylation at Lys9 and (4) are suppressed by mutations of Su(var)3-9. We propose that a reduced level of histone H4 acetylated at Lys12 by ATAC attenuates histone H3 phosphorylation at Ser10 by JIL-1 owing to reduced binding of JIL-1 to hypoacetylated chromatin.

The metazoan ATAC and SAGA coactivator HAT complexes regulate different sets of inducible target genes

“…In this respect, it is worth noting that dATAC was shown to play a role in histone H3S10 phosphorylation [45]. In ADA2a mutant flies, decreased histone acetylation led to consequent decrease in H3S10 phosphorylation by the JIL kinase [45]. Our novel observations show that the mammalian ATAC complex is also required for global H3S10 phosphorylation establishing a conserved link between ATAC function and H3S10 phophorylation during evolution.…”

“…In this respect, it is worth noting that dATAC was shown to play a role in histone H3S10 phosphorylation [45]. In ADA2a mutant flies, decreased histone acetylation led to consequent decrease in H3S10 phosphorylation by the JIL kinase [45].…”

“…As the Drosophila ATAC complex was shown to influence histone H3S10 phosphorylation [45], we have also tested whether ATAC-or SAGA specific knock-downs affect b Western blot analysis of the different fractions obtained during the purification shown in (a) using the indicated antibodies. c Acetylation of histone H3 and H4 tail peptides using the indicated purified complexes was measured.…”

DrosophilaCAF-1 regulates HP1-mediated epigenetic silencing and pericentric heterochromatin stability

“…For instance, H3S10 phosphorylation by JIL-1 prevents the spreading of H3K9 dimethylation, so that the chromatin acquires a euchromatic identity . Loss of acetylation of H4K12 impairs H3S10 phosphorylation and enhances the extension of H3K9 dimethylation (Ciurciu et al, 2008). Our finding that CAF-1 p180 genetically antagonizes JIL-1 during heterochromatin spreading suggests that CAF-1 p180 might function in late steps of the sequential heterochromatinization process, affecting histone modifications such as H3K9 methylation and H4K20 methylation.…”

Histone target selection within chromatin: an exemplary case of teamwork

“…Whereas depletion of the Atac2 HAT subunit in both mice and humans creates a loss of H3K9, H4K5, H4K12, and H4K16 acetylation (Guelman et al 2009), only H4K16ac is lost in flies (Suganuma et al 2008). Also, depletion of the Ada2 subunit leads to a decrease of H3K9ac and H3K14ac in HeLa cells (Nagy et al 2010), while its mutation in flies creates a drop in H4K12ac (Ciurciu et al 2008). Discrepancies have also been observed for the Ash1L methyltransferase (homolog of Drosophila Ash1).…”