test Browse by Author Names Browse by Titles of Works Browse by Subjects of Works Browse by Issue Dates of Works
       

Advanced Search
Home   
 
Browse   
Communities
& Collections
  
Issue Date   
Author   
Title   
Subject   
 
Sign on to:   
Receive email
updates
  
My Account
authorized users
  
Edit Profile   
 
Help   
About T-Space   

T-Space at The University of Toronto Libraries >
School of Graduate Studies - Theses >
Doctoral >

Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/32909

Title: Characterization of Baf60c in Mouse Heart Development
Authors: Sun, Xin
Advisor: Rossant, Janet
Bruneau, Benoit
Department: Molecular and Medical Genetics
Issue Date: 31-Aug-2012
Abstract: BAF (BRG1/Brm Associating Factors) complexes are ATP-dependent chromatin-remodeling complexes highly conserved from yeast to mammal. In mammals, the existence of tissue-specific BAF factors and their essential roles in the developmental processes suggest that they offer another layer of gene regulation control for mammalian development. Baf60c is one of the three Baf60s in the mouse. It expresses in the embryonic heart from E7.5 and later throughout the myocardium. To elucidate the role of Baf60c in mouse heart development, I constructed a Baf60c conditional knockout mouse line and characterize the Baf60c deletion phenotypes. Baf60c null embryonic hearts are hypoplastic and show abnormal contraction function and cardiomyocyte structural defects. Transcriptome analyses have identified gene groups critical for metabolism and contraction force generation. Deletion of Baf60c in myocardium at later development stages with Myh6::Cre results in severely dilated chambers, affecting the health and mortality. Echocardiography and electroncardiography have detected contraction and conduction defects in adult Baf60c myocardium deletion mice. Baf60c knockout cardiomyocyte also has disarrayed sarcomere. To elucidate the molecular mechanism by which Baf60c regulates cardiac gene expression, I detected the direct association of Baf60c with cardiac transcription factors Tbx5, Nkx2.5 and Myocardin. The transcription factor association domain is mapped to the N-terminal of Baf60c. To isolate the protein factors associated with Baf60c in vivo, I constructed a knock-in mouseline expressing epitope-tagged Baf60c. Expression of the tagged Baf60c was confirmed in ES cell differentiated cardiomyocyte and transgenic mice and its association with the other BAF complex members was also detected. In summary, my work has shown that the cardiac specific chromatin-remodeling factor Baf60c is an essential regulator for both embryonic heart and postnatal heart development. It may function through association with the cardiac transcription factors.
URI: http://hdl.handle.net/1807/32909
Appears in Collections:Doctoral

Files in This Item:

File Description SizeFormat
Sun_Xin_201206_PhD_thesis.pdf97.17 MBAdobe PDF
View/Open

Items in T-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

uoft