Title

A molecular and genetic analysis of the SNR1 subunit of the Brahma chromatin remodeling complex

Date of Award

2003

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Advisor(s)

Andrew K. Dingwall

Keywords

SNR1, Brahma, Chromatin, Brm

Subject Categories

Biochemistry, Biophysics, and Structural Biology | Genetics and Genomics | Life Sciences | Molecular Biology

Abstract

The Drosophila melanogaster Brahma (Brm) complex, a counterpart of the Saccharomyces cerevisiae SWI/SNF ATP-dependent chromatin remodeling complex, is a multi-protein complex important for proper development by maintaining specific gene expression patterns. The snr1 gene of Drosophila melanogaster encodes a conserved component of Brm complex. Loss-of-function and null mutations in the snr1 gene reveal its essential role in Drosophila development, while specific mutations in Ini1 , the human snr1 homolog, are associated with aggressive cancers, underscoring the importance of this particular subunit in development. This thesis focuses on a genetic and molecular analysis of the SNR1 subunit during Drosophila development, centering around the characterization and analysis of a temperature-sensitive allele of the snr1 gene, snr1 E1 . Genetic analyses of snr1 E1 reveal that it functions as an antimorph and that snr1 has critical roles in tissue patterning and growth control. Importantly, during wing vein formation in Drosophila , the SNR1 subunit appears to constrain the ATPase activities of the BRM subunit in maintaining or activating the expression of particular genes critical for proper vein formation to occur. Analysis of the SNR1 E1 protein in the context of Drosophila vein formation has therefore revealed an important regulatory function of SNR1 to activate or repress gene expression through specific associations with other members of the Brm complex.

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