The BCL6 transcriptional corepressor (BCOR) is mutated in the human
multisystemic developmental disorder Oculofaciocardiodental syndrome (OFCD). The
aim of this thesis is to understand the repressive function of BCOR in embryonic
development. To accomplish this, BCOR was first tandem affinity purified from human
embryonic kidney cells and found to interact with chromatin modifying proteins and
several transcription factors, suggesting a molecular mechanism by which BCOR effects
repression. In addition, conditional overexpression and null Bcor alleles were created in
mice to elucidate the in vivo role of BCOR. The conditional overexpression allele
revealed tight control of Bcor transcript levels in B cells and a requirement for proper
control of Bcor expression for embryonic viability. The conditional null allele revealed
that Bcor is required in neural crest cells for craniofacial development, in hindlimb
precursors for proper limb formation, and in cardiovascular progenitors for
cardiovascular development and function. These findings provide important insights into
the function of BCOR in embryonic development and will facilitate the future diagnosis
and treatment of developmental disorders such as OFCD.
University of Minnesota Ph.D. dissertation. May 2011. Major: Molecular, Cellular, Developmental Biology and Genetics. Advisor:Dr. Vivian June Bardwell. 1 computer file (PDF); vii, 166 pages.
Hamline, Michelle Yvonne.
The BCL6 transcriptional corepressor (BCOR) is required for multiple aspects of murine embryonic development..
Retrieved from the University of Minnesota Digital Conservancy,
Content distributed via the University of Minnesota's Digital Conservancy may be subject to additional license and use restrictions applied by the depositor.