The CHD family of ATP-dependent chromatin remodellers, which are present in all eukaryotes, utilise energy from the hydrolysis of ATP to alter nucleosome structure. The multiple CHD proteins have previously been implicated in transcription and developmental regulation, although the relationship between different family members is not well understood. The CHD family in H.sapiens contains nine proteins divided into three subfamilies. Whereas S.cerevisiae possess a single CHD, the Dictyostelium discoideum genome contains three CHD genes: one subfamily I member, related to human CHD1/2, and two subfamily III members, related to human CHD7/8. Dictyostelium fills a gap in the complexity scale, providing a smaller complement of CHD family members than mammalian models whilst still possessing a multicellular development stage and retaining a compact manipulatable genome. I have studied the expression patterns and created knockout mutants for all three Chd family members. The chd mutants have different developmental phenotypes that correlate with their expression profiles. RNA-seq analysis of the mutants showed that each Chd protein is responsible for regulating the expression of distinct classes of genes. Mapping nucleosomes genome wide in wild-type cells revealed that nucleosomes are structured similarly to higher eukaryotes. Mapping of nucleosomes in chdC-null suggested that ChdC regulates nucleosome repeat length in a subset of genes in a developmentally regulated manner. This thesis presents a comprehensive study of the Chd family in Dictyostelium and, to my knowledge, the first in vivo study of the nucleosome remodelling activity of a Chd subfamily III member.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:585341 |
| Date | January 2013 |
| Creators | Platt, James |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/53993/ |
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