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Journal article
Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain
Epigenetics, v 17(7), pp 786-807
03 Jul 2022
PMID: 34369292
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain
- Creators
- Mariah Beaver - Drexel UniversityBhanu Chandra KarisettyHaolin Zhang - Drexel UniversityAkanksha Bhatnagar - Drexel UniversityEllen Armour - Drexel UniversityVisha Parmar - Drexel UniversityReshma Brown - Drexel UniversityMerry Xiang - Drexel UniversityFelice Elefant - Drexel University
- Publication Details
- Epigenetics, v 17(7), pp 786-807
- Publisher
- Taylor & Francis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000683209500001
- Scopus ID
- 2-s2.0-85112071473
- Other Identifier
- 991019168710104721
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- Web of Science research areas
- Biochemistry & Molecular Biology
- Genetics & Heredity