Drosophila Epigenetics

Karnay, Ashley; Elefant, Felice

doi:10.1016/b978-0-12-805388-1.00014-6

Cited by 4 publications

(2 citation statements)

References 196 publications

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“…Our results support a model by which Mad, along with other TFs within a given gene body, serve as docking sites for recruitment of both HDAC2 and Tip60 either separately and within proximity to one another or simultaneously, thus keeping genes poised for rapid activation or repression. We speculate that these scenarios are not mutually exclusive of one another and, importantly, may explain the rapid histone acetylation changes within activitydependent neural genes that drive their swiftly fluctuating transcriptional responses [34,38,39]. Intriguingly, some of the TFs we identify have been previously implicated in AD.…”

Section: Discussionmentioning

confidence: 80%

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain

Beaver

Karisetty²,

Zhang

et al. 2021

Epigenetics

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Disruption of histone acetylation-mediated gene control is a critical step in Alzheimer's Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin (ChIP-seq) and transcriptional (RNA-seq) profiling study in Drosophila melanogaster brains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes. Moreover, AD brains exhibit robust genome-wide early alterations that include enhanced HDAC2 and reduced Tip60 binding and transcriptional dysregulation. Orthologous human genes to co-Tip60/HDAC2 D. melanogaster neural targets exhibit conserved disruption patterns in AD patient hippocampi. Notably, we discovered distinct transcription factor binding sites close or within Tip60/HDAC2 co-peaks in neuronal genes, implicating them in coenzyme recruitment. Increased Tip60 protects against transcriptional dysregulation and enhanced HDAC2 enrichment genome-wide. We advocate Tip60 HAT/HDAC2 mediated epigenetic neuronal gene disruption as a genome-wide initial causal event in AD.

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Section: Discussionmentioning

confidence: 80%

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain

Beaver

Karisetty²,

Zhang

et al. 2021

Epigenetics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our results support a model by which Mad, along with other TFs within a given gene body, serve as docking sites for recruitment of both HDAC2 and Tip60 either separately and within proximity to one another or simultaneously, thus keeping genes poised for rapid activation or repression. We speculate that these scenarios are not mutually exclusive of one another and, importantly, may explain the rapid histone acetylation changes within activity-dependent neural genes that drive their swiftly fluctuating transcriptional responses (Karnay & Elefant, 2017; Katan-Khaykovich & Struhl, 2002; Peserico & Simone, 2011). Intriguingly, some of the TFs we identify have been previously implicated in AD.…”

Section: Discussionmentioning

confidence: 98%

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain

Beaver

Karisetty

Zhang

et al. 2021

Preprint

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Disruption of histone acetylation mediated gene control is a critical step in Alzheimer's Disease (AD), yet chromatin analysis of antagonistic histone acetyltransferases (HATs) and histone deacetylases (HDACs) causing these alterations remains uncharacterized. We report the first Tip60 HAT versus HDAC2 chromatin and transcriptional profiling study in Drosophila brains that model early human AD. We find Tip60 and HDAC2 predominantly recruited to identical neuronal genes. Moreover, AD brains exhibit robust genome-wide early alterations that include enhanced HDAC2 and reduced Tip60 binding and transcriptional dysregulation. Orthologous human genes to co-Tip60/HDAC2 Drosophila neural targets exhibit conserved disruption patterns in AD patient hippocampi. Notably, we discovered distinct transcription factor (TF) binding sites within Tip60/HDAC2 co-peaks in neuronal genes, implicating them in co-enzyme recruitment. Increased Tip60 protects against transcriptional dysregulation and enhanced HDAC2 enrichment genome-wide. We advocate Tip60 HAT/HDAC2 mediated epigenetic neuronal gene disruption as a genome-wide initial causal event in AD.

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Investigating the genetic and epigenetic basis of big biological questions with the parthenogenetic marbled crayfish: A review and perspectives

Vogt

2018

J Biosci

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In the last 15 years, considerable attempts have been undertaken to develop the obligately parthenogenetic marbled crayfish Procambarus virginalis as a new model in biology. Its main advantage is the production of large numbers of offspring that are genetically identical to the mother, making this crustacean particularly suitable for research in epigenetics. Now, a draft genome, transcriptome and genome-wide methylome are available opening new windows for research. In this article, I summarize the biological advantages and genomic and epigenetic features of marbled crayfish and, based on first promising data, discuss what this new model could contribute to answering of ''big'' biological questions. Genome mining is expected to reveal new insights into the genetic specificities of decapod crustaceans, the genetic basis of arthropod reproduction, moulting and immunity, and more general topics such as the genetic underpinning of adaptation to fresh water, omnivory, biomineralization, sexual system change, behavioural variation, clonal genome evolution, and resistance to cancer. Epigenetic investigations with the marbled crayfish can help clarifying the role of epigenetic mechanisms in gene regulation, tissue specification, adult stem cell regulation, cell ageing, organ regeneration and disease susceptibility. Marbled crayfish is further suitable to elucidate the relationship between genetic and epigenetic variation, the transgenerational inheritance of epigenetic signatures and the contribution of epigenetic phenotype variation to the establishment of social hierarchies, environmental adaptation and speciation. These issues can be tackled by experiments with highly standardized laboratory lineages, comparison of differently adapted wild populations and the generation of genetically and epigenetically edited strains.

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Drosophila Epigenetics

Cited by 4 publications

References 196 publications

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain

Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain

Investigating the genetic and epigenetic basis of big biological questions with the parthenogenetic marbled crayfish: A review and perspectives

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