ORCID
https://orcid.org/0009-0004-5125-0621
Date of Award
Spring 2026
Language
English
Embargo Period
5-8-2028
Document Type
Master's Thesis
Degree Name
Master of Science (MS)
College/School/Department
Department of Biological Sciences
Program
Biology
First Advisor
Soma Dash
Committee Members
Melinda Larsen, Aya Osman
Keywords
Med23, Mediator complex, craniofacial development, neural crest cells, chromatin accessibility, single-nucleus ATAC-seq
Subject Categories
Bioinformatics | Developmental Biology
Abstract
Craniofacial development requires tightly regulated gene expression programs that control neural crest cell proliferation, migration, and differentiation. The Mediator complex plays a key role in transcription by helping transcription factors regulate gene expression. Med23, a subunit of this complex, is essential for craniofacial development, as conditional deletion of Med23 in mouse neural crest cells leads to craniofacial defects. However, the regulatory mechanism through which Med23 influences gene expression during craniofacial development remain unclear.
To investigate whether Med23 influences chromatin accessibility at genes involved in craniofacial development, snATAC-seq data from E11.5 whole embryo heads from Med23fx/fx;Wnt1-Cre mutant mice were analyzed. snATAC-seq analysis revealed that chromatin accessibility changes were not changed uniformly distributed across cell populations. While osteogenic and chondrogenic populations exhibited differential accessibility associated with developmental pathways, the osteochondroprogenitor population showed minimal changes, suggesting that Med23 does not broadly regulate chromatin accessibility at early progenitor stages. Differential accessibility analysis identified regions associated with developmental pathways, including skeletal system development and regulation of cartilage development. Since, cartilage and bone formation are key components of craniofacial development, Sox9 and Runx2 were examined as candidate transcription factors that may regulate these pathways.
ChIP-nexus datasets from E11.5 branchial arches were then analyzed to identify genes associated with Sox9 and Runx2 binding. Gene ontology analysis of Sox9-associated genes revealed enrichment for RNA processing and developmental signaling pathways, supporting a role for Sox9 in coordinating transcriptional and post-transcriptional regulation during craniofacial development. In contrast, Runx2-associated genes were enriched for cell cycle and mitotic processes, indicating a role for Runx2 in regulating proliferation and differentiation of osteogenic precursors.
Integration of snATAC-seq and ChIP-nexus datasets demonstrated that Sox9 and Runx2 binding sites largely overlap with accessible chromatin regions in both control and mutant samples, with minimal difference between conditions. Comparison of the ATAC-seq and ChIP-seq datasets identifies several overlapping genes associated with both chromatin accessibility and transcription factor binding, highlighting candidate genes that may be regulated by Sox9 and Runx2.
Together, these findings suggest that Med23 does not primarily function to establish chromatin accessibility but instead regulates transcriptional output at already accessible regions. This supports a model in which Med23 acts as a transcriptional co-regulator, integrating transcription factor to control lineage-specific gene expression programs during craniofacial development.
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Fofana, Aminata N., "Inside the Regulatory Switchboard: Med23 & the Control of Developmental Gene Programs" (2026). Electronic Theses & Dissertations (2024 - present). 492.
https://scholarsarchive.library.albany.edu/etd/492