Crystal structure of the histone acetyltransferase Hpa2: a tetrameric member of the Gcn5-related N-acetyltransferase superfamily

Angus-Hill, Melinda L.; Dutnall, Robert; Tafrov, Stefan T.; Sternglanz, Rolf; Ramakrishnan, V.

doi:10.1006/jmbi.1999.3338

Cited by 98 publications

(94 citation statements)

References 35 publications

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“…Hpa2p acetylates histones H3 and H4 in vitro with a preference for Lys14 of histone H3 shared by Gcn5p (Angus-Hill et al 1999), and Hpa3p shares 49% sequence identity and 81% sequence similarity with Hpa2p. We observed that deletion of these genes was not lethal in an hsl7D mutant strain ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

Chromatin-Modifiying Enzymes Are Essential When the Saccharomyces cerevisiae Morphogenesis Checkpoint Is Constitutively Activated

Ruault

Pillus

2006

Genetics

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Hsl7p plays a central role in the morphogenesis checkpoint triggered when yeast bud formation is impaired and is proposed to function as an arginine methyltransferase. HSL7 is also essential in the absence of the N-terminal tails of histones H3 or H4. The requirement for H3 and H4 tails may indicate a need for their post-translational modification to bypass the morphogenesis checkpoint. In support of this, the absence of the acetyltransferases Gcn5p or Esa1p, the deacetylase Rpd3p, or the lysinemethyltransferase Set1p resulted in death or extreme sickness in hslD mutants. These synthetic interactions involved both the activity of the chromatin-modifying enzymes and the complexes through which they act. Newly reported silencing phenotypes of hsl7D mirror those previously reported for gcn5D and rpd3D, thereby strengthening their functional links. In addition, synthetic interactions and silencing phenotypes were suppressed by inactivation of the morphogenesis checkpoint, either by SWE1 deletion or by preventing Cdc28p phosphorylation. A catalytically dead Hsl7p retained wild-type interactions, implying that modification of histone H3 or H4 N termini by Gcn5p, Esa1p, Rpd3p, and Set1p, but not by Hsl7p, was needed to bypass the morphogenesis checkpoint.

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Section: Resultsmentioning

confidence: 99%

Chromatin-Modifiying Enzymes Are Essential When the Saccharomyces cerevisiae Morphogenesis Checkpoint Is Constitutively Activated

Ruault

Pillus

2006

Genetics

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“…Some HATs have been shown to preferentially acetylate histones on specific lysine residues. For example, the HATs HPA2 and Gcn5 appear to preferentially acetylate histone H3 on Lys-14, a residue that has been implicated in regulation of transcription (9,10). Histone acetylation appears to increase transcription initiation by facilitating the binding of transcription factors and the RNA polymerase II enzyme holoenzyme to DNA (11,12).…”

Section: From the Baylor College Of Medicine Department Of Neurosciementioning

confidence: 99%

Regulation of Histone Acetylation during Memory Formation in the Hippocampus

Levenson

O’Riordan

Brown

et al. 2004

Journal of Biological Chemistry

1,023

999

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Formation of long term memory begins with the activation of many disparate signaling pathways that ultimately impinge on the cellular mechanisms regulating gene expression. We investigated whether mechanisms regulating chromatin structure were activated during the early stages of long term memory formation in the hippocampus. Specifically, we investigated hippocampal histone acetylation during the initial stages of consolidation of long term association memories in a contextual fear conditioning paradigm. Acetylation of histone H3 in area CA1 of the hippocampus was regulated in contextual fear conditioning, an effect dependent on activation of N-methyl-D-aspartic acid (NMDA) receptors and ERK, and blocked using a behavioral latent inhibition paradigm. Activation of NMDA receptors in area CA1 in vitro increased acetylation of histone H3, and this effect was blocked by inhibition of ERK signaling. Moreover, activation of ERK in area CA1 in vitro through either the protein kinase C or protein kinase A pathways, biochemical events known to be involved in long term memory formation, also increased histone H3 acetylation. Furthermore, we observed that elevating levels of histone acetylation through the use of the histone deacetylase inhibitors trichostatin A or sodium butyrate enhanced induction of long term potentiation at Schaffer-collateral synapses in area CA1 of the hippocampus, a candidate mechanism contributing to long term memory formation in vivo. In concert with our findings in vitro, injection of animals with sodium butyrate prior to contextual fear conditioning enhanced formation of long term memory. These results indicate that histone-associated heterochromatin undergoes changes in structure during the formation of long term memory. Mimicking memory-associated changes in heterochromatin enhances a cellular process thought to underlie long term memory formation, hippocampal long term potentiation, and memory formation itself.

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“…A number of acetyltransferases have been identified in Saccharomyces cerevisiae that acetylate histones in vitro , and in vivo (Kuo et al 1998;Zhang et al 1998). The majority of these HATs show discrete substrate specificities, including the GCN5-dependent SAGA, ADA, and HAT-A2 complexes (Grant et al 1997;Ruiz-Garcia et al 1997;Saleh et al 1997;Eberharter et al 1999), the SAS3-dependent NuA3 complex (John et al 2000), the Nut1p containing mediator complex (Lorch et al 2000), the ESA1-dependent NuA4 complex (Smith et al 1998;Allard et al 1999;Clarke et al 1999), and Hpa2p, a protein that to date has only been characterized in recombinant form (Angus-Hill et al 1999). Gcn5p and Hpa2p are members of the GNAT family of acetyltransferases, and acetylate preferentially Lys 14 of histone H3 in free histones in vitro (Kuo et al 1996;Tse et al 1998;AngusHill et al 1999).…”

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confidence: 99%

Histone H3 specific acetyltransferases are essential for cell cycle progression

Howe¹,

Auston²,

Grant³

et al. 2001

Genes Dev.

209

187

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Longstanding observations suggest that acetylation and/or amino-terminal tail structure of histones H3 and H4 are critical for eukaryotic cells. For Saccharomyces cerevisiae, loss of a single H4-specific histone acetyltransferase (HAT), Esa1p, results in cell cycle defects and death. In contrast, although several yeast HAT complexes preferentially acetylate histone H3, the catalytic subunits of these complexes are not essential for viability. To resolve the apparent paradox between the significance of H3 versus H4 acetylation, we tested the hypothesis that H3 modification is essential, but is accomplished through combined activities of two enzymes. We observed that Sas3p and Gcn5p HAT complexes have overlapping patterns of acetylation. Simultaneous disruption of SAS3, the homolog of the MOZ leukemia gene, and GCN5, the hGCN5/PCAF homolog, is synthetically lethal due to loss of acetyltransferase activity. This key combination of activities is specific for these two HATs because neither is synthetically lethal with mutations of other MYST family or H3-specific acetyltransferases. Further, the combined loss of GCN5 and SAS3 functions results in an extensive, global loss of H3 acetylation and arrest in the G 2 /M phase of the cell cycle. The strikingly similar effect of loss of combined essential H3 HAT activities and the loss of a single essential H4 HAT underscores the fundamental biological significance of each of these chromatin-modifying activities.

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Crystal structure of the histone acetyltransferase Hpa2: a tetrameric member of the Gcn5-related N-acetyltransferase superfamily

Cited by 98 publications

References 35 publications

Chromatin-Modifiying Enzymes Are Essential When the Saccharomyces cerevisiae Morphogenesis Checkpoint Is Constitutively Activated

Chromatin-Modifiying Enzymes Are Essential When the Saccharomyces cerevisiae Morphogenesis Checkpoint Is Constitutively Activated

Regulation of Histone Acetylation during Memory Formation in the Hippocampus

Histone H3 specific acetyltransferases are essential for cell cycle progression

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