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Identification of Twist1 Target Genes in Mesenchymal Cell Populations

Lee, Mary P
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378394058

Abstract Details

2013, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
Precise temporal and spatial regulation of gene expression is critical for proper embryo development. Alterations in gene expression can lead to congenital malformations and later development of diseases such as cancer. The basic helix-loop-helix transcription factor Twist1 has been shown to regulate cell migration, proliferation, and specification, and to maintain an undifferentiated state in various cell types during development. Mutations in human TWIST1 lead to Saethre-Chotzen syndrome, in which patients show limb defects and premature differentiation of cranial sutures. Re-expression of Twist1 during postnatal life is observed in pediatric and adult diseased heart valves and many types of metastatic cancers. Twist1 function has been explored during both development and disease, however, the direct transcriptional targets of Twist1 are still largely unknown. In endocardial cushion (ECC) mesenchymal cells of the developing heart valves, Twist1 promotes cell proliferation and migration. The studies here identify five direct transcriptional targets of Twist1 in ECC mesenchymal cells, Tbx20, Cdh11, Sema3C, Rab39b, and Gadd45a. Whether Twist1 binds the same regulatory regions in different cell types during development or in development versus disease is unknown. Therefore, a comparison of Twist1 binding was performed at a genome-wide level by chromatin immunoprecipitation followed by sequencing (ChIP-seq) analysis in two developmental tissues (ECCs and limb buds) and a cancer cell line (peripheral nerve sheath tumor (PNST) cells). Little overlap of Twist1 binding peaks between cell types was observed, indicating cell type-specific transcriptional regulation. Although Twist1 binding sites are not shared in different cell types the downstream cellular functions are conserved. Studies in this dissertation further elucidate the transcriptional targets and molecular mechanism utilized by Twist1 during heart valve development, limb, and in PNST cells that will aid in understanding normal developmental processes and disease progression.
Katherine Yutzey, Ph.D. (Committee Chair)
Linda Parysek, Ph.D. (Committee Member)
Nancy Ratner, Ph.D. (Committee Member)
Stephanie Ware, M.D., Ph.D. (Committee Member)
Susanne Wells, Ph.D. (Committee Member)
188 p.
Molecular Biology
Twist1; Gene regulation; endocardial cushions; limb buds; peripheral nerve sheath tumors; ChIP seq

Recommended Citations

Citations

  • Lee, M. P. (2013). Identification of Twist1 Target Genes in Mesenchymal Cell Populations [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378394058

    APA Style (7th edition)

  • Lee, Mary. Identification of Twist1 Target Genes in Mesenchymal Cell Populations. 2013. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378394058.

    MLA Style (8th edition)

  • Lee, Mary. "Identification of Twist1 Target Genes in Mesenchymal Cell Populations." Doctoral dissertation, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1378394058

    Chicago Manual of Style (17th edition)

ucin1378394058
228
© 2013, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.