The Mechanism Of Regulation Of Autosomal Heterochromatic Genes In drosophila Melanogaster Males By rox Rna And Msl Proteins

<p>In humans and flies, males and females have different set of sex chromosomes contributing to different levels of X-linked gene expression. To equalize X-linked gene dosage between sexes, both humans and flies developed independent strategies which are called dosage compensation. Human females randomly inactivate one of their X chromosome into barr body and <i>Drosophila</i> males up regulate their single X chromosome two fold. Both strategies equalize of X linked gene dose between sexes. </p> <p>In <i>Drosophila</i>, dosage compensation is brought about by the ribonucleoprotein Male Specific Lethal (MSL) complex that binds hundreds of sites along the X chromosome and modifies chromatin to facilitate transcription. Loss of <i>roX</i> RNA, an essential component of the MSL complex, reduces expression from X-linked genes. Surprisingly, loss of <i>roX</i> RNA also reduces expression from genes situated in proximal heterochromatin and on the small, heterochromatic 4^th chromosome. Reduction of <i>roX</i> function suppresses position effect variegation (PEV), revealing functional alteration in heterochromatin. The effects of <i>roX</i> mutations on heterochromatic gene expression and PEV are limited to males. We proposed that <i>roX</i> and some MSL proteins have an additional role in regulation of heterochromatic genes. </p> <p>Microarray analysis of male larva that are mutant for MSL2, a male limited member of the MSL complex, showed that MSL2 is not required for heterochromatic gene regulation, revealing that intact MSL complex is not required for heterochromatic gene regulation. Examination of remaining MSL proteins using qRT-PCR showed that MSL1, MSL3, MOF and MLE, but not Jil-1 kinase, contribute to heterochromatic gene expression. </p> <p>To determine if different regions of <i>roX</i> are required for dosage compensation and heterochromatic silencing, examination of both processes with a panel of <i>roX</i> deletions showed that <i>roX</i> functions are partially separable by some mutations and <i>roX</i> has regions that are required for its heterochromatic function, but not for dosage compensation.</p> <p>Chromatin immunoprecipitation of staged embryos revealed that MSL3 binds to autosomal genes, and to genes in heterochromatic regions, prior to the onset of dosage compensation, suggesting a direct role at these sites. These findings support the idea that several MSL complex members participate in additional complexes that target distinct sets of genes.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Open Access Dissertation

Discipline thesis:degree_discipline

Biological Sciences

Year dc:date.available

2014

Author dc:creator

• Koya, Satya Kiran

Contributors dc:contributor

• Victoria H. Meller

• Dosage compensation
• Global gene regulation
• Heterochromatin
• MSL proteins
• Position Effect Variegation
• roX RNA
• Biology
• Genetics
• Molecular Biology

Repository record dc:identifier

https://digitalcommons.wayne.edu/oa_dissertations/895

OAI identifier oai:identifier

oai:digitalcommons.wayne.edu:oa_dissertations-1894