Date of Graduation


Document Type

Dissertation (PhD)

Program Affiliation

Genes and Development

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Michelle Barton, Ph.D.

Committee Member

Gary Gallick, Ph.D.

Committee Member

Pierre McCrea, Ph.D.

Committee Member

Xiaobing Shi, Ph.D.

Committee Member

Jessica Tyler, Ph.D.


In this dissertation, I discovered that function of TRIM24 as a co-activator

of ERα-mediated transcriptional activation is dependent on specific histone

modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first

part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated

histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.

Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of

TRIM24-regulated ERα target genes is greatly impaired. Importantly, I

demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen

responsive elements (EREs) in a time-dependent manner upon estrogen

induction, and depletion of their expression exert corresponding time-dependent

effect on target gene activation. I also identified that phosphorylation of histone

H3 threonine T6 disrupts TRIM24 from binding to the chromatin and from

activating ERα-regulated targets. In the second part, I revealed that TRIM24

depletion has additive effect to LSD1 inhibitor- and Tamoxifen-mediated

reduction in survival and proliferation in breast cancer cells.


TRIM24, LSD1, H3K4 methylation, epigenetics, estrogen receptor, transcription



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