Abstract

Brain development requires exquisite control of gene expression to establish and refine the proper circuitry of the nervous system. Gene expression control is under the purview of several cellular processes, including chromatin regulation in the form of DNA modification, histone modification, and nucleosome remodeling. Chromatin remodeling enzymes are the major effectors of nucleosome remodeling. These enzymes are clearly involved in brain development – mutations in chromatin remodeling enzymes are likely causative for neurodevelopmental disorders of cognition. Chromatin remodeling enzymes have discrete molecular functions and binding profiles and similarly control distinct phases of nervous system maturation. Chd4 is a Chd family chromatin remodeling enzyme that is mutated in Sifrim-Hitz-Weiss intellectual disability syndrome and is critical for neuronal differentiation. Chd4 binds to active regulatory elements, including promoters and enhancers, to putatively restrict genomic accessibility and repress gene expression. Work on Chd4 in the brain has revealed pathways of gene regulation that impact gene promoters, but the function of Chd4 at enhancers, and their effects on promoters through three-dimensional genomic interactions, in the developing brain remains poorly understood.

Committee Chair

Azad Bonni Harrison Gabel

Committee Members

Azad Bonni, Harrison W. Gabel, Aaron DiAntonio, Milan G. Chheda,

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Molecular Genetics & Genomics)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

Spring 5-15-2021

Language

English (en)

Author's ORCID

http://orcid.org/0000-0003-2235-5673

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