Mapping Global Histone Acetylation Patterns to Gene Expression

Abstract

Histone acetyltransferases and deacetylases with specificities for different sites of acetylation affect common chromatin regions. This could generate unique patterns of acetylation that may specify downstream biological processes. To search for existence of these patterns and their relationship to gene activity, we analyzed the genome-wide acetylation profiles for eleven lysines in the four core histones of Saccharomyces cerevisiae. We find that both hyper- and hypoacetylation of individual lysines are associated with transcription, generating distinct patterns of acetylation that define groups of biologically related genes. The genes within these groups are significantly coexpressed, mediate similar physiological processes, share unique cis-regulatory DNA motifs, and are enriched for binding of specific transcription factors. Our data also indicate that the in vivo binding of the transcription factor Bdf1 is associated with acetylation on most lysines but relative deacetylation on H4 lysine 16. Thus, certain acetylation patterns may be used as surfaces for specific protein-histone interactions, providing one mechanism for coordinate regulation of chromatin processes that are biologically related.

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

“…K16Ac correlates with active and open chromatin and colocalizes in most cases with other acetylated histone tail residues such as H4K8 and -H4K12, H3K9 and H3K14 and H2BK11 and H2BK16 (Kurdistani et al, 2004). It is also found with the active transcription mark H3K4me3 in chromatin from yeast to humans (Millar et al, 2006;O'Neill et al, 2006).…”

“…It is also found with the active transcription mark H3K4me3 in chromatin from yeast to humans (Millar et al, 2006;O'Neill et al, 2006). However, H4K16 acetylation antagonizes some other acetylated residues like H2BK18 and methylated residues like H3K79 (Kurdistani et al, 2004, Vaquero et al, 2004, H3K9 (Vaquero et al, 2004;O'Neill et al, 2006), H4K20me1 (Vaquero et al, 2004), H3K27 (Rougeulle et al, 2004), and probably H4 sumoylation and arginine methylation Nathan et al, 2006). Yet, there is some evidence that suggests the coexistence of monoacetyl K16 and H4K20me2,3 within the same H4 tail.…”

INO80 subfamily of chromatin remodeling complexes

“…Who is the reader for this "histone code"? Bdf1, the shared component of SWR1 and TFIID complexes bearing two bromodomans, is a good candidate, because it selectively binds acetylated forms of histone H4 [99]. More importantly, Bdf1 occupancy was positively correlated with Htz1 occupancy in the genome [82], as deletion of either Bdf1 alone or Bdf1 and its redundant homolog, Bdf2, resulted in significant reductions in Htz1 recruitment [82,83], indicating that Bdf1 is required for efficient H2AZ deposition.…”

De la régulation du génome à la progression tumorale

“…De nombreuses études, fondées notamment sur des immunoprécipitations de la chromatine (ChIP) avec pour intermédiaires des anticorps spécifiques de la queue H4 acétylée (parfois d'une position donnée), couplées à des analyses d'expression des gènes, ont été menées pour élucider l'effet de l'acétylation sur le processus de transcription. Certaines études ont non seulement fourni la cartographie et la description des portions acétylées de différents génomes, mais, de plus, elles ont démontré que dans les régions promotrices des gènes transcrits les histones étaient globalement hyper-acétylées [14,15]. Toutefois, ces études n'ont pas permis de corréler les niveaux de transcription à l'acétylation d'une lysine donnée de H4, probablement à cause d'une redondance entre lysines, mais plus simplement, dans la plupart des cas, par suite de l'absence d'étude cinétique du processus d'initiation de la transcription.…”