Histone H4-K16 Acetylation Controls Chromatin Structure and Protein Interactions

Abstract

Acetylation of histone H4 on lysine 16 (H4-K16Ac) is a prevalent and reversible posttranslational chromatin modification in eukaryotes. To characterize the structural and functional role of this mark, we used a native chemical ligation strategy to generate histone H4 that was homogeneously acetylated at K16. The incorporation of this modified histone into nucleosomal arrays inhibits the formation of compact 30-nanometer-like fibers and impedes the ability of chromatin to form cross-fiber interactions. H4-K16Ac also inhibits the ability of the adenosine triphosphate-utilizing chromatin assembly and remodeling enzyme ACF to mobilize a mononucleosome, indicating that this single histone modification modulates both higher order chromatin structure and functional interactions between a nonhistone protein and the chromatin fiber.

HDAC1 and HDAC2 in mouse oocytes and preimplantation embryos: Specificity versus compensation

“…46 Acetylation of H4K16 inhibits formation of the higher order 30 nm chromatin structure, and loss of H4K16 shows defects equivalent to the loss of the H4 tails. 69 The increased acetylation of H4K16 observed in Hdac2-deficient oocytes likely contributes to the failure of chromosomes to condense fully during oocyte maturation and compromised kinetochore function in mutant eggs, because reducing H4K16 acetylation by overexpressing HDAC2 in Hdac2 −/− oocytes restores normal chromosome condensation and segregation. 46 A recent report also provides further evidence that H4K16 deacetylation has an important role in maintaining normal chromatin structure in oocyte maturation; H4K16 hyperacetylation induced by knockdown of SIRT2, a member of Class III HDACs, leads to spindle defects, missegregation of chromosome and impaired kinetochore-microtubule interaction.…”

The vitamin D receptor in cancer

“…The apo and holo nuclear receptor complexes initiate specific and coordinated histone modifications (69,70) to govern transcriptional responsiveness of the promoter. There is good evidence that specific histone modifications also determine the assembly of transcription factors on the promoter and control individual promoter transcriptional responsiveness (71)(72)(73) . It is less clear to what extent nuclear receptors recognize basal histone modifications on target gene promoters; functional studies of the SANT motif contained in the co-repressor NCoR2/SMRT support this latter idea (74) .…”

Males absent on the first (MOF): from flies to humans

“…Evidence for this mechanism comes from the finding that histone hyperacetylation is known to increase the accessibility of nucleosomal DNA to transcription factors and other co-activators in budding yeast (Anderson et al, 2001). Furthermore, elegant in vitro studies have shown that synthetic acetylation of H4 at K16 alone is sufficient to inhibit the formation of condensed 30 nm chromatin fibers and cross-fiber interactions (Shogren-Knaak et al, 2006). A second model is founded on the fact that certain protein motifs are able to recognize specifically chemically modified histone tails.…”