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.

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