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Title page for ETD etd-07072008-144634


Type of Document Dissertation
Author Chandler, Kelly Jane
URN etd-07072008-144634
Title Identification of an ancient Bmp4 cis-regulatory element using fish and mouse
Degree PhD
Department Molecular Physiology and Biophysics
Advisory Committee
Advisor Name Title
Maureen Gannon Committee Chair
E. Michelle Southard-Smith Committee Member
Ela Knapik Committee Member
Linda Sealy Committee Member
Richard O'Brien Committee Member
Keywords
  • Bone morphogenetic proteins
  • Mesoderm
  • Enhancer
  • Cis-Regulatory Element
  • Bmp4
Date of Defense 2008-03-10
Availability unrestricted
Abstract
Bone morphogenetic protein 4 (Bmp4) is a multi-functional, developmentally regulated gene and is essential for early mouse development. Little is known about the transcriptional regulation of Bmp4. To investigate the hypothesis that Bmp4 utilizes numerous long-range cis-regulatory elements to direct its repertoire of spatiotemporal expression patterns, we surveyed a 398 kilobase region of the Bmp4 locus for transcriptional activity. Our findings indicate multiple tissue-specific cis-regulatory elements reside greater than 28 kilobases 5' or 3' to the mouse Bmp4 transcription unit. We used comparative analyses to identify three noncoding sequences conserved across 450 million years of evolution that reside ~50-100 kilobases from the Bmp4 promoter and are maintained in a syntenic group across vertebrates. One of three ancient noncoding sequences reproducibly directed lacZ expression in embryonic mesoderm. Taken together, these experiments indicate an ancient, mesoderm-specific Bmp4 cis-regulatory element resides nearly 50 kilobases 5' to mouse Bmp4.
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