The CLAMP protein is essential in Drosophila in mediating dosage compensation through increased targeting to the X-chromosome and during development as a non-sex specific transcription factor. Soruco, Marcela creator 2014 24, 214 p. born digital Thesis (Ph.D. -- Brown University (2014) Erica, Larschan Director Mark, Johnson Reader Robert, Reenan Reader Nicola, Neretti Reader Fred, Winston Reader Brown University. BIOMED: Molecular Biology, Cell Biology, and Biochemistry sponsor theses Dosage compensation in Drosophila is a valuable model for studying how transcription complexes are targeted throughout the genome because all of the genes along the length of a single chromosome are identified for co-regulation. In Drosophila, dosage compensation is mediated by the Male Specific Lethal (MSL) complex, which increases transcript levels of X-linked genes in males approximately two-fold to equalize expression levels with the two X chromosomes in females as well as with autosomes. It is thought that the MSL complex identifies the X chromosome in multiple steps. First, the roX loci are though to be targeted which encode the two non-coding RNA components of complex. Next, in a sequence dependent step, a series of high affinity sites containing cis-acting GA-rich MSL Recognition Elements (MRE) are targeted. Finally, sequence-independent spreading of the MSL complex occurs along the X chromosome through the recognition of specific histone modifications association with active transcription. Recently, we identified a previously unstudied zinc finger protein, Chromatin-linked adaptor for MSL proteins (CLAMP), as a key regulator of Drosophila dosage compensation. CLAMP is able to directly target MRE sequences and is enriched at MSL high affinity sites on the X chromosome including the roX loci. Enrichment of CLAMP at the roX loci could identify them as “seed sites” for MSL recruitment that initiates the X-identification cascade. CLAMP is found at the promoters of many active genes in male and female cells, is an essential protein in both males and females and is therefore not a sex-specific factor. To investigate CLAMP as a genome wide transcription factor, we analyzed a fly line containing a P-element insertion and performed mRNA-seq in male and female cells. Using the P-element insertion fly line, we uncovered a new role for CLAMP in development where decreased CLAMP levels caused sever viability and motor defects in male and females with males being very sensitive to the loss of CLAMP. Using mRNA-seq, we found CLAMP regulating genes involved in neuromuscular development. Understanding how the non-sex specific function and the dosage compensation function of CLAMP is integrated is critical in understanding how dosage compensation evolved in Drosophila dosage compensation gene regulation Genetic regulationTranscription factors RPB 20141006 engEnglish10.7301/Z04B2ZNMIn CopyrightCollection is open for research.dissertations