The Experts below are selected from a list of 39180 Experts worldwide ranked by ideXlab platform
Ted Abel - One of the best experts on this subject based on the ideXlab platform.
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acetyl coa synthetase regulates Histone Acetylation and hippocampal memory
Nature, 2017Co-Authors: Philipp Mews, Greg Donahue, Adam M Drake, Vince Luczak, Ted Abel, Shelley L ErgeAbstract:Metabolic production of acetyl coenzyme A (acetyl-CoA) is linked to Histone Acetylation and gene regulation, but the precise mechanisms of this process are largely unknown. Here we show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) directly regulates Histone Acetylation in neurons and spatial memory in mammals. In a neuronal cell culture model, ACSS2 increases in the nuclei of differentiating neurons and localizes to upregulated neuronal genes near sites of elevated Histone Acetylation. A decrease in ACSS2 lowers nuclear acetyl-CoA levels, Histone Acetylation, and responsive expression of the cohort of neuronal genes. In adult mice, attenuation of hippocampal ACSS2 expression impairs long-term spatial memory, a cognitive process that relies on Histone Acetylation. A decrease in ACSS2 in the hippocampus also leads to defective upregulation of memory-related neuronal genes that are pre-bound by ACSS2. These results reveal a connection between cellular metabolism, gene regulation, and neural plasticity and establish a link between acetyl-CoA generation 'on-site' at chromatin for Histone Acetylation and the transcription of key neuronal genes.
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The Role of Histone Acetylation in Long-Term Memory Storage
Research and Perspectives in Neurosciences, 2012Co-Authors: Shane G. Poplawski, Ted AbelAbstract:Long-term contextual memory formation requires transcription within the hippocampus, a brain structure deep inside the medial temporal lobe. The mechanisms by which this transcription is initiated and maintained are still poorly understood, although Histone Acetylation is known to be involved. The interaction between phosphorylated CREB and the Histone acetyltransferase CREB-binding protein (CBP) is necessary for long-term memory. Histone Acetylation is known to increase at specific CREB regulated promoters after contextual fear conditioning, and Histone deacetylase (HDAC) inhibitors, which increase Histone Acetylation, have been demonstrated to increase long-term memory when injected into the hippocampus during memory consolidation. Specific lysine residues on Histone tails are targets for Acetylation, and individual Acetylation patterns may be important regulators of long-term memory. Determining the genes regulated by Histone Acetylation after contextual learning will provide insight into the necessary components of memory consolidation and may lead to development of novel, selective therapeutics that enhance memory in diseases in which memory is affected.
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The Role of Histone Acetylation in Memory Formation and Cognitive Impairments
Neuropsychopharmacology, 2012Co-Authors: Lucia Peixoto, Ted AbelAbstract:Long-term memory formation requires transcription and protein synthesis. Over the past few decades, a great amount of knowledge has been gained regarding the molecular players that regulate the transcriptional program linked to memory consolidation. Epigenetic mechanisms have been shown to be essential for the regulation of neuronal gene expression, and Histone Acetylation has been one of the most studied and best characterized. In this review, we summarize the lines of evidence that have shown the relevance of Histone Acetylation in memory in both physiological and pathological conditions. Great advances have been made in identifying the writers and erasers of Histone Acetylation marks during learning. However, the identities of the upstream regulators and downstream targets that mediate the effect of changes in Histone Acetylation during memory consolidation remain restricted to a handful of molecules. We outline a general model by which corepressors and coactivators regulate Histone Acetylation during memory storage and discuss how the recent advances in high-throughput sequencing have the potential to radically change our understanding of how epigenetic control operates in the brain.
Paule Latino-martel - One of the best experts on this subject based on the ideXlab platform.
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Modulation of Histone Acetylation by garlic sulfur compounds.
Anti-Cancer Agents in Medicinal Chemistry, 2011Co-Authors: Nathalie Druesne-pecollo, Paule Latino-martelAbstract:Preclinical studies have shown that fresh garlic extracts, aged garlic, garlic oil and specific organosulfur compounds generated by processing garlic could alter carcinogen metabolism, inhibit tumor cell growth through induction of cell cycle arrest or apoptosis, or angiogenesis. In particular, recent studies have suggested that anticarcinogenic effects of certain garlic compounds may implicate at least in part a modulation of Histone Acetylation, a process involved in the regulation of gene expression, resulting from the inhibition of Histone deacetylase activity. The aim of this review is to describe available data on sulfur compounds from garlic and Histone Acetylation and to discuss their potential for cancer prevention. Available data indicate that garlic compounds could inhibit Histone deacetylase activity and induce Histone hyperAcetylation in vitro as well as in vivo. Sparse studies provide evidence of an involvement of Histone Acetylation in modulation of gene expression by diallyl disulfide and allyl mercaptan. These effects were observed at high concentrations. Further investigations are needed to determine if the HDAC inhibitory effects of garlic organosulfur compounds might play a role in primary cancer prevention at doses achievable by human diet.
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Modulation of Histone Acetylation by Garlic Sulfur Compounds
Anti-Cancer Agents in Medicinal Chemistry, 2011Co-Authors: Nathalie Pecollo, Paule Latino-martelAbstract:Preclinical studies have shown that fresh garlic extracts, aged garlic, garlic oil and specific organosulfur compounds generated by processing garlic could alter carcinogen metabolism, inhibit tumor cell growth through induction of cell cycle arrest or apoptosis, or angiogenesis. In particular, recent studies have suggested that anticarcinogenic effects of certain garlic compounds may implicate at least in part a modulation of Histone Acetylation, a process involved in the regulation of gene expression, resulting from the inhibition of Histone deacetylase activity. The aim of this review is to describe the available data on sulfur compounds from garlic and Histone Acetylation and to discuss their potential for cancer prevention. Available data indicate that garlic compounds could inhibit Histone deacetylase activity and induce Histone hyperAcetylation both in vitro as well as in vivo. Sparse studies provide evidence of involvement of Histone Acetylation in modulation of gene expression by diallyl disulfide and allyl mercaptan. These effects were observed at high concentrations. Further investigations are needed to determine if the HDAC inhibitory effects of garlic organosulfur compounds play a role in primary cancer prevention at doses achievable by human diet.
Siavash K Kurdistani - One of the best experts on this subject based on the ideXlab platform.
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Regulators of Cellular Levels of Histone Acetylation in Saccharomyces cerevisiae
Genetics, 2008Co-Authors: Weimin Peng, Cynthia I Togawa, Kangling Zhang, Siavash K KurdistaniAbstract:Histone Acetylation levels are regulated through the opposing activities of Histone acetyltransferases (HATs) and deacetylases (HDACs). While much is known about gene-specific control of Histone Acetylation, little is understood about how total or cellular levels of Histone Acetylation are regulated. To identify regulators of cellular levels of Histone Acetylation, we developed an immunofluorescence-based approach to screen the single-gene deletion library of Saccharomyces cerevisiae for strains with significant reductions in cellular Histone Acetylation levels. Of the 4848 mutants screened, we identified 63 strains with considerable cellular hypoAcetylation of N-terminal lysines in Histones H3 and H4. The cellular hypoAcetylation was validated for subsets of the identified strains through secondary screens including mass spectrometric analysis of individual lysines and chromatin immunoprecipitation of specific genomic loci. Among the identified mutants were several members of the Ccr4-Not complex, V-type ATPases, and vacuolar protein-sorting complexes as well as genes with unknown functions. We show that Gcn5, a major HAT in yeast, has diminished Histone acetyltransferase activity in particular mutants, providing a plausible explanation for reduction of cellular Acetylation levels in vivo. Our findings have revealed unexpected and novel links between Histone Acetylation, Gcn5 HAT activity, and diverse processes such as transcription, cellular ion homeostasis, and protein transport.
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Histone Acetylation and deAcetylation in yeast
Nature Reviews Molecular Cell Biology, 2003Co-Authors: Siavash K Kurdistani, Michael GrunsteinAbstract:Histone Acetylation and deAcetylation in the yeast Saccharomyces cerevisiae occur by targeting acetyltransferase and deacetylase enzymes to gene promoters and, in an untargeted and global manner, by affecting most nucleosomes. Recently, new roles for Histone Acetylation have been uncovered, not only in transcription but also in DNA replication, repair and heterochromatin formation. Interestingly, specific acetylatable lysines can function as binding sites for regulatory factors. Moreover, Histone deAcetylation is not only repressive but can be required for gene activity.
Michael Grunstein - One of the best experts on this subject based on the ideXlab platform.
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Histone Acetylation and deAcetylation in yeast
Nature Reviews Molecular Cell Biology, 2003Co-Authors: Siavash K Kurdistani, Michael GrunsteinAbstract:Histone Acetylation and deAcetylation in the yeast Saccharomyces cerevisiae occur by targeting acetyltransferase and deacetylase enzymes to gene promoters and, in an untargeted and global manner, by affecting most nucleosomes. Recently, new roles for Histone Acetylation have been uncovered, not only in transcription but also in DNA replication, repair and heterochromatin formation. Interestingly, specific acetylatable lysines can function as binding sites for regulatory factors. Moreover, Histone deAcetylation is not only repressive but can be required for gene activity.
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Genomewide Histone Acetylation microarrays.
Methods, 2003Co-Authors: Daniel Robyr, Michael GrunsteinAbstract:Histone Acetylation and methylation are important regulators of gene activity. Chromatin immunoprecipitation (ChIP or ChrIP) has made it possible to examine not only the state of Histone Acetylation at a gene but also that of Histone methylation and may soon be extended to other Histone modifications such as phosphorylation and ubiquitination. In principle such studies are possible as long as an antibody is available to the particular Histone modification. Once a target gene is identified it is instructive to see the effect of mutating putative enzymes responsible for the modification to determine how a particular enzyme is responsible for altering chromatin of that gene. Although specific target genes have been studied that contain such modifications recent technical advances have made it possible to study Histone modifications genomewide. This not only allows for alternate views of particular paradigms to be investigated, but also uncovers chromosomal patterns of Histone modification that would be missed in analyzing individual genes. We describe here an approach to rapidly study Histone modifications genomewide by combining chromatin immunoprecipitation and DNA microarrays.
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Histone Acetylation regulates the time of replication origin firing
Molecular Cell, 2002Co-Authors: Maria Vogelauer, Liudmilla Rubbi, Isabelle Lucas, Bonita J Brewer, Michael GrunsteinAbstract:The temporal firing of replication origins throughout S phase in yeast depends on unknown determinants within the adjacent chromosomal environment. We demonstrate here that the state of Histone Acetylation of surrounding chromatin is an important regulator of temporal firing. Deletion of RPD3 Histone deacetylase causes earlier origin firing and concurrent binding of the replication factor Cdc45p to origins. In addition, increased Acetylation of Histones in the vicinity of the late origin ARS1412 by recruitment of the Histone acetyltransferase Gcn5p causes ARS1412 alone to fire earlier. These data indicate that Histone Acetylation is a direct determinant of the timing of origin firing.
Andrew J Andrews - One of the best experts on this subject based on the ideXlab platform.
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interaction with the dna repair protein thymine dna glycosylase regulates Histone Acetylation by p300
Biochemistry, 2016Co-Authors: Ryan A Henry, Rossella Tricarico, Pietro Mancuso, Marc Tini, Philip A. Cole, Alfonso Bellacosa, Andrew J AndrewsAbstract:How protein–protein interactions regulate and alter Histone modifications is a major unanswered question in epigenetics. The Histone acetyltransferase p300 binds thymine DNA glycosylase (TDG); utilizing mass spectrometry to measure site-specific changes in Histone Acetylation, we found that the absence of TDG in mouse embryonic fibroblasts leads to a reduction in the rate of Histone Acetylation. We demonstrate that TDG interacts with the CH3 domain of p300 to allosterically promote p300 activity to specific lysines on Histone H3 (K18 and K23). However, when TDG concentrations approach those of Histones, TDG acts as a competitive inhibitor of p300 Histone Acetylation. These results suggest a mechanism for how Histone Acetylation is fine-tuned via interaction with other proteins, while also highlighting a connection between regulators of two important biological processes: Histone Acetylation and DNA repair/demethylation.
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Changing the selectivity of p300 by acetyl-CoA modulation of Histone Acetylation.
ACS Chemical Biology, 2014Co-Authors: Ryan A Henry, Yin-ming Kuo, Vikram Bhattacharjee, Tim J. Yen, Andrew J AndrewsAbstract:Determining how Histone Acetylation is regulated is vital for treating the many diseases associated with its misregulation, including heart disease, neurological disorders, and cancer. We have previously reported that acetyl-CoA levels alter p300 Histone Acetylation in a site-specific manner in vitro. Here, we further investigate how changing acetyl-CoA concentrations alter the Histone Acetylation pattern by altering p300 specificity. Interestingly, these changes are not a simple global change in Acetylation, but rather site specific changes, whereby Acetylation at some sites increase while others decrease. We also demonstrate how the p300 inhibitor C646 can pharmacologically alter p300 Histone Acetylation patterns in vitro and in cells. This study provides insight into the mechanisms regulating p300 residue specificity, a potential means for altering p300 dependent Histone Acetylation, and an investigation into altering Histone Acetylation patterns in cells.