Genome-wide analysis of SAS-I-mediated H4 K16 acetylation
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE19962 | GEO | 2012/01/18
SECONDARY ACCESSION(S): PRJNA122611
REPOSITORIES: GEO
Similar Datasets
Project description:The MYST HAT Sas2 is part of the SAS-I complex. The target for acetylation by Sas2 is Lys16 of histone H4 (H4 K16Ac). This acetylation site marks euchromatic regions and opposes the spreading of heterochromatin at telomere-proximal regions. Changes of SAS-I-mediated H4 K16Ac on a genome-wide scale comparing wt and sas2M-bM-^HM-^F cells were investigated in this study. We found a pronounced, genome-wide loss of H4 K16 acetylation in the body of transcribed genes in the absence of Sas2. Furthermore, the influence of Sas2 on gene expression was investigated in RNA expression arrays. H4 K16Ac and H4 in wt and sas2M-bM-^HM-^F was ChIPed. ChIP experiments were performed three times with independent chromatin preparations.
2012-01-18 | E-GEOD-19962 | biostudies-arrayexpress
Project description:Genome-wide analysis of SAS-I-mediated H4 K16 acetylation
2011-01-26 | E-TABM-901 | biostudies-arrayexpress
Project description:The histone acetyltransferase Sas2 is part of the SAS-I complex and acetylates lysine 16 of histone H4 (H4 K16Ac) in the genome of Saccharomyces cerevisiae. Sas2-mediated H4 K16Ac is strongest over the coding region of genes with low expression. However, it is unclear how Sas2-mediated acetylation is incorporated into chromatin. Our previous work has shown physical interactions of SAS with the histone chaperones CAF-I and Asf1, suggesting a link between SAS-I mediated acetylation and chromatin assembly. Here, we find that Sas2-dependent H4 K16Ac in bulk histones requires passage of the cells through the S-phase of the cell cycle, and the rate of increase in H4 K16Ac depends on both CAF-I and Asf1, whereas steady-state levels and genome-wide distribution of H4 K16Ac shows only mild changes in their absence. Furthermore, H4 K16Ac is deposited in chromatin at genes upon repression, and this deposition requires the histone chaperone Spt6, but not CAF-I, Asf1, HIR or Rtt106. Altogether, our data indicate that Spt6 controls H4 K16Ac levels by incorporating K16-unacetylated H4 in strongly transcribed genes. Upon repression, Spt6 association is decreased, resulting in less deposition of K16-unacetylated and therefore in a concomitant increase of H4 K16Ac that is recycled during transcription.
2015-09-14 | E-MTAB-2638 | biostudies-arrayexpress
Project description:Genome-wide analysis of SAS-I-mediated H4 K16 acetylation
| PRJNA122611 | ENA
Project description:Several MYST-family histone acetyltransferase (HAT) enzymes associate with specific ING tumor suppressor proteins. ING complexes containing the HBO1 HAT protein are the major source of histone H4 acetylation in vivo and have been shown to play critical roles in gene regulation and DNA replication. Here, we present a molecular dissection of HBO1/ING HAT complexes that unravels the protein domains required for complex assembly and function. A distinctive characteristic of ING HAT complexes is the presence of multiple PHD finger domains in different subunits. Biochemical and functional analysis of these domains indicate that they interact with histone H3 N-terminal tail region but with different specificity towards the methylation status of lysine 4. They play essential and intricate role in regulating binding to chromatin and substrate specificity. This is achieved in part through expression of subunit isoforms controlling which PHD fingers are present in the complex. Importantly, localization analysis on the human genome indicate that HBO1 complexes are enriched throughout the coding region of genes, supporting a role in transcription elongation. These results also underline the importance and versatility of PHD finger domains in regulating chromatin association and trans-histone acetylation specificity within a single protein complex. ChIP-chip of FLAG-JADE1 +/- doxorubicin treatment in Hela cells
2010-05-14 | E-GEOD-14309 | biostudies-arrayexpress
Project description:ESA1 (essential SAS-family acetyltransferase) is the only known yeast histone acetyltransferase (HAT) required for cell viability. It is a member of the MYST (MOZ, YBF2/SAS3, SAS2, Tip60) family of HAT proteins and contains a conserved acetyltransferase domain in addition to a chromodomain. While ESA1âs HAT activity is important in processes such as deoxyribonucleic acid (DNA) repair, acetylation is likely not its essential function. Our lab has shown that mutants with a single point mutation in the active site cysteine are still viable even though their acetyltransferase abilities are abolished. Furthermore, chromatin immunoprecipitation assays have shown ESA1 distributed evenly along the length of chromatin, not localized to specific promoters as would be expected from a HAT protein involved in transcriptional regulation. As is the case for other HAT proteins, ESA1âs acetyltransferase activity is significant, but in processes such as DNA replication, DNA repair and cell cycle progression. The aim of this project is to determine the essential function of ESA1 - the catalytic subunit of the yeast HAT complex, NuA4 (nucleosome acetyltransferase of H4) â using a bypass suppression screen to identify suppressors of ESA1. It is proposed that suppressing mutations will alter a gene involved in the process that is the essential function of ESA1. Thus, identifying a suppressor that can bypass the need for ESA1 may provide insight into its essential function. Since ESA1 is an essential gene, a haploid esa1â strain in which wild-type ESA1 is provided on a centromeric plasmid was utilized. The bypass suppression screen resulted in suppressors of ESA1 that allowed esa1â cells to be viable even in the absence of the essential gene. These second site suppressors (sup-) of ESA1 each show the Mendelian segregation pattern of the suppressing gene and ESA1 in 2:2 ratios, implying they are single genes unlinked to ESA1. Microarray and nuclear morphology studies show abnormal gene expression and morphology of the esa1ï sup- cells, further implicating the suppressing mutation in DNA repair and replication processes. Investigating ESA1âs essential role and a probable conservation of function across species can provide a deeper understanding of the capabilities of HAT complexes. Experiment Overall Design: Eight samples were analyzed. The only variables are the ESA1 and SUP2 genes. WT (ESA1 SUP2), 2 replicates. Single mutant (ESA1 sup2-), 3 replicates. Double mutant (esa1 sup2-), 3 replicates.
2008-06-16 | E-GEOD-9840 | biostudies-arrayexpress
Project description:Histone acetyltransferases (HAT) assemble into multisubunit complexes in order to target distinct lysine residues on nucleosomal histones. Here, we characterize native HAT complexes assembled by the BRPF-family of scaffold proteins. Their PHD-ZnKnuckle-PHD domain is essential for binding chromatin and restricted to unmethylated H3K4, a specificity that is reversed by the associated ING subunit. Native BRPF1 complexes can contain either MOZ/MORF or HBO1 as catalytic acetyltransferase subunit. Interestingly, while the previously reported HBO1 complexes containing JADE scaffold proteins target histone H4, the HBO1-BRPF1 complex acetylates only H3 in chromatin. We mapped a small region at the N-terminus of scaffold proteins responsible for histone tail selection on chromatin. Thus, alternate choice of subunits associated with HBO1 can switch its specificity from H4 to H3 tails, highlighting a crucial new role of associated subunits within HAT complexes, previously thought to be intrinsic to the catalytic subunit. Genome-wide mapping of MYST acetyltransferases subunits and H3K4me3 histone mark in RKO cells.
2013-10-09 | E-GEOD-47190 | biostudies-arrayexpress
Project description:Several MYST-family histone acetyltransferase (HAT) enzymes associate with specific ING tumor suppressor proteins. ING complexes containing the HBO1 HAT protein are the major source of histone H4 acetylation in vivo and have been shown to play critical roles in gene regulation and DNA replication. Here, we present a molecular dissection of HBO1/ING HAT complexes that unravels the protein domains required for complex assembly and function. A distinctive characteristic of ING HAT complexes is the presence of multiple PHD finger domains in different subunits. Biochemical and functional analysis of these domains indicate that they interact with histone H3 N-terminal tail region but with different specificity towards the methylation status of lysine 4. They play essential and intricate role in regulating binding to chromatin and substrate specificity. This is achieved in part through expression of subunit isoforms controlling which PHD fingers are present in the complex. Importantly, localization analysis on the human genome indicate that HBO1 complexes are enriched throughout the coding region of genes, supporting a role in transcription elongation. These results also underline the importance and versatility of PHD finger domains in regulating chromatin association and trans-histone acetylation specificity within a single protein complex.
2009-01-09 | GSE14309 | GEO
Project description:To better understand the role of histone lysine acetylation in transcription in Plasmodium falciparum, we sought to attenuate the histone acetyltransferase (HAT) activity of PfGCN5 using anacardic acid (AA). We showed that AA reversibly and noncompetitively inhibited the HAT activity of recombinant PfGCN5. To a lesser extent, AA inhibited the PfGCN5 activity in parasite nuclear extracts, but did not affect the histone deacetylase activity. AA blocked the growth of both chloroquine-sensitive and -resistant strains with a 50% inhibitory concentration of ~30 uM. Treatment of the parasites with 20 uM of AA for 12 h had no obvious effect on parasite growth or gross morphology, but induced hypoacetylation of histone H3 at K9 and K14, but not H4 at K5, K8, K12, and K16, suggesting of specific inhibition of the PfGCN5 HAT. Microarray analysis showed that this AA treatment disturbed the parasite transcription program, resulting in â¥2-fold change in the expression of 271 (~5%) parasite genes in late trophozoites, among which 207 genes were down-regulated. Interestingly, a significant proportion of the down-regulated genes is potentially associated with signal transduction and transcription. Furthermore, cluster analysis of gene expression indicated that AA mostly down-regulated active genes, and this gene pool significantly overlapped with that enriched for H3K9 acetylation. We further demonstrated by chromatin immunoprecipitation and real-time polymerase chain reaction that AA treatment reduced acetylation near the putative promoters of a set of down-regulated genes. The identification of AA as a PfGCN5 inhibitor offers a useful tool for further functional analysis of epigenetics in transcription regulation in malaria parasites. Late trophozoits were selected after AA treatment or untreated for RNA extraction and hybridization on microarrays. We sought to obtain the expression level changing after AA treatment.
2008-06-13 | E-GEOD-11763 | biostudies-arrayexpress
Project description:Changes in acetylation of histone H4 are a common hallmark of cancer cells. In leukemia cells, histone H4 is characterized by loss of K16 mono-acetylation. Bromodomain proteins specifically recognize acetylated lysines and have been used as a target for anti cancer drug, JQ1 and iBET. Although acetylation and de-acetylation of histone H4 have been shown to have big impact in cancer cells, little attention has been focused on histone H4-acetylation at a genome level. To uncover potential epigenetic role of hyper-acetylated histone H4 at a genome-wide level in cancer cell, we generated a novel monoclonal antibody specifically recognizing histone H4 with at least two acetylated lysine residues (H4K5ac+K8ac). At the genome-wide level, hyper-acetylated histone H4 is associated with promoter and regulatory element (active enhancer, eRNA and super enhancer). We show that diacetylation at K5 and K8 of histone H4 co-localizes H3K27ac and BRD2 in the majority of active enhancer and promoters. However BRD2 has a stronger association with H4K5acK8ac. Furthermore we identified two specific chromatin states, which separately contain either H3K27ac or acetylated histone H4. Although JQ1 led to global reduction of BRD2 binding on the chromatin, only local changes of histone H4 multi-acetylation were observed upon BET inhibition by JQ1
2018-06-04 | GSE113714 | GEO