Characterisation of SUMV-1, a novel nuclear protein in 𝘊𝘢𝘦𝘯𝘰𝘳𝘩𝘢𝘣𝘥𝘪𝘵𝘪𝘴 𝘦𝘭𝘦𝘨𝘢𝘯𝘴 potentially involved in chromatin regulation
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USyd Access
Type
ThesisThesis type
Doctor of PhilosophyAuthor/s
Hoe, MatthewAbstract
Chromatin regulation is an important process in the developmental control of gene expression. In the nematode Caenorhabditis elegans the developmental role of chromatin regulation has been explored in several contexts, including vulval development. Synthetic multivulva (synMuv) ...
See moreChromatin regulation is an important process in the developmental control of gene expression. In the nematode Caenorhabditis elegans the developmental role of chromatin regulation has been explored in several contexts, including vulval development. Synthetic multivulva (synMuv) genes are regulators of vulval development and encode components of several histone modification and chromatin remodelling complexes. synMuv genes prevent inappropriate vulval induction by repressing the ectopic expression of a necessary developmental signal. In synMuv mutant worms, the developmental signal is no longer repressed, leading to development of ectopic vulvae. In this work a mutation in a gene named suppressor of synthetic multivulva-1 (sumv-1) was found to suppress ectopic vulval induction in synMuv mutant worms. Additionally, reduction of function of SUMV-1 suppressed ectopic expression of the vulval induction signal. Literature searches revealed that SUMV-1 had previously been found to interact with a related protein I have named SUMV-2. Whilst many mammalian proteins involved in chromatin regulation have homologues in C. elegans, there remain some without a worm homologue. Analysis of the SUMV-1 and SUMV-2 protein sequences found them to be similar to two mammalian proteins which are components of a histone acetyltransferase complex. A chromatin-associated domain was identified in SUMV-1. Protein interaction studies revealed a third protein, MYS-2, which interacted with SUMV-2. MYS-2 shared sequence similarity to another member of the mammalian histone acetyltransferase complex. Reduction of function of both SUMV-2 and MYS-2 also suppressed the synMuv phenotype, suggesting that SUMV-1, SUMV-2, MYS-2 could be core components of a worm histone acetyltransferase complex which regulates gene expression during development. These studies highlight the utility of C. elegans as a model organism to study chromatin regulation.
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See moreChromatin regulation is an important process in the developmental control of gene expression. In the nematode Caenorhabditis elegans the developmental role of chromatin regulation has been explored in several contexts, including vulval development. Synthetic multivulva (synMuv) genes are regulators of vulval development and encode components of several histone modification and chromatin remodelling complexes. synMuv genes prevent inappropriate vulval induction by repressing the ectopic expression of a necessary developmental signal. In synMuv mutant worms, the developmental signal is no longer repressed, leading to development of ectopic vulvae. In this work a mutation in a gene named suppressor of synthetic multivulva-1 (sumv-1) was found to suppress ectopic vulval induction in synMuv mutant worms. Additionally, reduction of function of SUMV-1 suppressed ectopic expression of the vulval induction signal. Literature searches revealed that SUMV-1 had previously been found to interact with a related protein I have named SUMV-2. Whilst many mammalian proteins involved in chromatin regulation have homologues in C. elegans, there remain some without a worm homologue. Analysis of the SUMV-1 and SUMV-2 protein sequences found them to be similar to two mammalian proteins which are components of a histone acetyltransferase complex. A chromatin-associated domain was identified in SUMV-1. Protein interaction studies revealed a third protein, MYS-2, which interacted with SUMV-2. MYS-2 shared sequence similarity to another member of the mammalian histone acetyltransferase complex. Reduction of function of both SUMV-2 and MYS-2 also suppressed the synMuv phenotype, suggesting that SUMV-1, SUMV-2, MYS-2 could be core components of a worm histone acetyltransferase complex which regulates gene expression during development. These studies highlight the utility of C. elegans as a model organism to study chromatin regulation.
See less
Date
2017-03-31Licence
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.Faculty/School
Faculty of Science, School of Life and Environmental SciencesAwarding institution
The University of SydneyShare