Dissertations, Theses, and Capstone Projects
Date of Degree
9-2023
Document Type
Dissertation
Degree Name
Ph.D.
Program
Biochemistry
Advisor
Patrizia Casaccia
Committee Members
Jill Bargonetti
Mark Emerson
Guillermo Gerona-Navarro
James E. Goldman
Subject Categories
Biochemistry | Cell Biology | Developmental Neuroscience | Molecular and Cellular Neuroscience
Keywords
histone, brain, chromatin, development, transcriptome
Abstract
Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid metabolism genes. Pharmacological inhibition of enzymes depositing H4K8ac in aOPCs reduces the levels of these transcripts, rendering them more similar to nOPCs. Overall, our results identify the H4K8ac histone mark as an important regulator of the transcriptional activation of oligodendrocyte stage-specific genes in aOPCs.
Recommended Citation
Dansu, David K., "Changes in the Epigenetic Landscape of Oligodendrocyte Progenitor Cells with Time" (2023). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/5503
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Biochemistry Commons, Cell Biology Commons, Developmental Neuroscience Commons, Molecular and Cellular Neuroscience Commons