Date of Award

2023

Degree Type

Thesis

Degree Name

Master of Arts (MA)

Department

Microbiology, Molecular Biology and Biochemistry

First Advisor

Master of Arts (MA)

Abstract

The COMPASS-like family of lysine methyltransferases, MLR/MLX complexes, are epigenetic regulators that are essential for normal development through the methylation of the fourth lysine residue on histone 3 (H3K4), a universal epigenetic mark associated with active transcription. This family of complexes is highly conserved from yeast to mammals and the genes encoding the human MLR complexes have been associated with various developmental diseases and cancers (Dingwall and Fagan, 2019). In D. melanogaster, the enzymatic methyltransferase core of this complex is composed of two proteins: Cara Mitad (Cmi, also known as Lpt) and Trithorax-related (Trr). Although these proteins have been shown to be crucial for proper development, little is known about their function in regulating transcription in early animal development. My research shows that Cmi localizes to chromatin coordinately with the activation of zygotic transcription. This contrasts with the female germline where Cmi can be found on the oocyte pronucleus at even the earliest stages of oogenesis and is propagated through later stages of oocyte development. Moreover, we have shown that loss of Cmi disrupts epigenetic marking of chromosomes in the developing oocyte as shown by a reduction of HK27ac, H3K27me3, and H3K4me1 marks on the oocyte pronucleus upon Cmi depletion. Analysis of Cmi knockdown embryos containing an eve-LacZ reporter transgene revealed that loss of Cmi leads to disrupted transcriptional activation in early embryogenesis. Together, this work implicates the requirement of MLR complex for proper transcriptional activation in early development.

Creative Commons License

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

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