Date of Award

2018

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Molecular and Cellular Biochemistry Program

Abstract

The MLR family of COMPASS-like complexes are histone methyltransferase complexes that are associated with the activation of gene enhancers. In D. melanogaster, Cara mitad (Cmi, also known as Lpt) and Trithorax related (Trr) are central subunits of a complex orthologous to mammalian Lysine methyltransferase 2 C and D (KMT2C and KMT2D, also known as MLL3 and MLL2/4) that catalyze H3K4 monomethylation. Previous studies have demonstrated that mutations in these genes are associated with cancer and developmental disorders, but the mechanisms by which these alterations contribute to disease states are unknown. The Cmi-containing COMPASS-like complex and orthologous vertebrate complexes have been identified as necessary co-regulators of multiple critical developmental signaling pathways, and knockout experiments have demonstrated that these complexes are necessary for development and viability. My research shows that Cmi has a distinct expression pattern in developing tissues, and the knockdown abrogates normal developmental patterns in both the embryo and ovary. Ubiquitous shRNA mediated knockdown of Cmi in the embryo results in early embryonic lethality, and shRNA expressed in certain ovary tissues results in reduced egg-laying efficiency and incomplete ovary development. By elucidating the embryogenesis stage at which the COMPASS-like complex performs its function as well as its requirement in the female germline, future experiments aimed at revealing gene targets can be narrowed to these key developmental periods.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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