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Hox Specificity: Constrained vs. Flexible Requirements for the PBC and MEIS Cofactors

Uhl, Juli D.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1397234792

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
The Hox factors are a highly conserved family of transcription factors, well known for patterning the anterior-posterior axis during embryonic development. The Hox transcription factors control target gene expression by directly interacting with enhancers. Paradoxically, an individual Hox factor is expressed in a broad region yet generates cell- and tissue-specific transcriptional outcomes. Despite concerted effort, we still lack complete understanding of the mechanisms underlying Hox specificity. However, several Hox co-factors have been identified, notably two classes of TALE homeodomain factors, PBC (Drosophila Exd, vertebrate Pbx) and MEIS (Drosophila Hth, vertebrate Meis/Prep), which form DNA-bound complexes with Hox factors. At the start of this project, it was known that any Hox factor could form a cooperative complex with the PBC and/or MEIS factors and that these complexes increased specificity and affinity of Hox for DNA. The focus of this project was to understand how Hox, PBC, and MEIS binding site arrangements and complex formation affected gene regulation. It was not clear whether each Hox factor differentially required PBC- and/or MEIS-DNA binding for robust complex formation. Second, it was unknown if certain Hox/PBC/MEIS binding site arrangements correlated with strength of Hox complex formation or if certain arrangements were differentially associated with groups of Hox factors. Finally, it was unclear whether differential affinity could alter Hox output.
Brian Gebelein, Ph.D. (Committee Chair)
Steven Potter, Ph.D. (Committee Member)
Nadean Brown, Ph.D. (Committee Member)
Kenneth Campbell, Ph.D. (Committee Member)
Iain Cartwright, Ph.D. (Committee Member)
191 p.
Molecular Biology
Hox; Exd; Hth; cis-regulatory module; CRM; Transcription

Recommended Citations

Citations

  • Uhl, J. D. (2014). Hox Specificity: Constrained vs. Flexible Requirements for the PBC and MEIS Cofactors [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1397234792

    APA Style (7th edition)

  • Uhl, Juli. Hox Specificity: Constrained vs. Flexible Requirements for the PBC and MEIS Cofactors. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1397234792.

    MLA Style (8th edition)

  • Uhl, Juli. "Hox Specificity: Constrained vs. Flexible Requirements for the PBC and MEIS Cofactors." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1397234792

    Chicago Manual of Style (17th edition)

ucin1397234792
204
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This open access ETD is published by University of Cincinnati and OhioLINK.