Epigenetic modulation of epithelial-mesenchymal plasticity through chromatin modifiers KDM6A and CTCF.

Johnson, Kelsey S., 1993-

Epigenetic modulation of epithelial-mesenchymal plasticity through chromatin modifiers KDM6A and CTCF.

dc.contributor.advisor	Taube, Joseph H.
dc.creator	Johnson, Kelsey S., 1993-
dc.date.accessioned	2022-06-03T13:12:55Z
dc.date.available	2022-06-03T13:12:55Z
dc.date.created	2022-05
dc.date.issued	2022-04-22
dc.date.submitted	May 2022
dc.date.updated	2022-06-03T13:12:56Z
dc.description.abstract	Epithelial-mesenchymal transition (EMT) and its reversal, mesenchymal-epithelial transition (MET) drive tissue reorganization critical for early development. In carcinomas, processing through EMT promotes migration, invasion, dormancy, and metastatic colonization. As a reversible process, EMT is inherently regulated at epigenetic and epigenomic levels. To understand the epigenomic nature of EMT, we characterized chromatin accessibility dynamics, transcriptomic output, protein expression, and cellular phenotypes during stepwise reversible EMT. We find that KDM6A and CTCF are suppressed and re-expressed, coincident with dynamic H3K27me3 and broad alterations in chromatin accessibility, during EMT/MET. These two factors are also lower in triple-negative breast cancer cell lines with EMT features. Through analysis of chromatin accessibility we identify that early EMT is characterized by enrichment for AP-1 family member binding motifs but also by diminished enrichment for CTCF binding motifs. Through loss-of-function analysis we demonstrate that suppression of CTCF strengthens the epithelial phenotype via upregulation of epithelial markers E-cadherin/CDH1, and downregulation of N-cadherin/CDH2. Conversely, upregulation of CTCF leads to upregulation of EMT gene expression and an increase in mesenchymal traits. These findings are indicative of a role of CTCF in regulating epithelial-mesenchymal gene expression.
dc.format.mimetype	application/pdf
dc.identifier.uri	https://hdl.handle.net/2104/11899
dc.language.iso	en
dc.rights.accessrights	No access – contact librarywebmaster@baylor.edu
dc.subject	Chromatin. Cell plasticity. Cancer.
dc.title	Epigenetic modulation of epithelial-mesenchymal plasticity through chromatin modifiers KDM6A and CTCF.
dc.type	Thesis
dc.type.material	text
local.embargo.lift	2024-05-01
local.embargo.terms	2024-05-01
thesis.degree.department	Baylor University. Dept. of Biology.
thesis.degree.grantor	Baylor University
thesis.degree.level	Doctoral
thesis.degree.name	Ph.D.