Joyce Pieretti

The evolution of the cis-regulatory architecture surrounding key developmental genes is a major contributor to the phenotypic evolution of complex traits. One approach to exploring this phenomenon involves phylogenetic functional studies of gene regulation across distantly related species. This method identifies signatures of conserved non-coding elements (CNEs) that may be of functional significance and determines how changes in cis-regulatory elements or transcription factors influence gene expression patterns. These analyses help to elucidate the evolution of regulatory architecture across species. Sonic hedgehog (Shh), and the protein it encodes, plays an indispensible role in vertebrate development. This trans-dev gene contributes to a variety of structures, including the forebrain, limbs, and oral cavity, among others. The Shh locus contains a complex assembly of regulatory elements that control the abundance, duration, and location of gene expression in these structures. Despite the identification of these regulatory elements in limited vertebrate systems, little has been done to explore how well conserved the Shh regulatory architecture is across large phylogenetic distances. With greater evolutionary time more changes can accumulate in CNEs, potentially modifying patterns of gene expression. This gap in our knowledge fails to provide a clear picture of how changes in regulatory architecture can impact phenotypic evolution. To gain a more comprehensive understanding of the transcriptional regulatory evolution of the Shh locus, I investigate and characterize the function of several Shh CNEs using transgenesis in order to detect patterns of conservation and/or divergence of regulation driving Shh expression in both common structures likes the urogenital tract, and novel structures such as the tetrapod limb and mammalian epiglottis.

Publications

Li, F. Yan, Y., Pieretti, J., Feldman, D.A., Eckhardt, L.E. (2010). Comparison of Identical and Functional Igh Alleles Reveals a Nonessential Role for Eµ in Somatic Hypermutation and Class-Switch Recombination. Journal of Immunology. doi:10.4049/jimmunol.0902992.

Yan, Y., Pieretti J., Christin J., Bah, F., Eckhardt, L.E. (2011). Homologous elements hs3a and hs3b in the 3' regulatory region of the murine immunoglobulin heavy chain (Igh) locus are both dispensable for class-switch recombination. The Journal of Biological Chemistry 286: 27123-27131.

Back to people