Interaction of the DNA -Bound Estrogen Receptor With Coregulatory Proteins

Estrogen receptors (ERs) alpha and beta are members of a large family of transcription factors that regulate gene expression in response to estrogen. Although the role of ligand in altering coactivator recruitment and transcription has been well documented, the effect of DNA-binding on coregulator recruitment has not been addressed. On binding to the estrogen response elements (EREs) in the target genes the ERs undergo DNA-induced changes in conformation. This study investigates the role of DNA-induced receptor conformations on coregulator recruitment. Here we have documented an ERE-dependent recruitment of coactivator proteins, amplified in breast cancer (AIB1) and transcription intermediary factor (TIF2) to ERalpha and ERbeta. In our efforts to identify novel interactions with the DNA-bound receptor, we have isolated several proteins that interact with the A2 ERE-bound ERalpha using DNA pull-down and agarose gel shift assays. Identification of the components of these complexes reveal proteins involved in several cell processes including, transcription, DNA repair and replication, G-protein modulation, and scavengers of superoxide radicals. Investigation of the association of ERalpha with the DNA repair protein, 3-methyadenine DNA glycosylase (MPG) reveals that this interaction modulates estrogen responsiveness and alters DNA repair. Taken together, these studies demonstrate multiple roles ER plays at the promoter. The DNA-bound receptor is involved in differential recruitment of coactivator proteins and is associated with proteins involved in other processes integrating various cell signals to modulate ER-mediated transcription.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Likhite, Varsha Sharad

Contributors dc:contributor

• Nardulli, Ann M.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3101903

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84799