Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Chromatin and transcriptomic profiling uncover dysregulation of the Tip60 HAT/HDAC2 epigenomic landscape in the neurodegenerative brain Disruption of histone acetylation mediated gene control is a critical step in Alzheimers 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.
14
The categories of this paper are: biophysics
18
The categories of this paper are: systems
26
The categories of this paper are: biochemistry
10
The categories of this paper are: and
15
The categories of this paper are: developmental
4
The categories of this paper are: neuroscience
9
The categories of this paper are: synthetic
16
The categories of this paper are: microbiology
27
The categories of this paper are: pathology
24
The categories of this paper are: cancer
19
The categories of this paper are: epidemiology
17
The categories of this paper are: molecular
6
The categories of this paper are: plant
30
The categories of this paper are: scientific
22
The categories of this paper are: physiology
29
The categories of this paper are: education