Regulation of Myc and its Localization to Histone Locus Body in Drosophila
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University of North Carolina at Charlotte
Myc is a transcriptional factor required for normal growth and development in vertebrates and invertebrates alike. Loss of function mutations in Myc can cause embryonic lethality in mammals and larval death in flies whereas an increase in its activity can lead to tumorigenesis. Therefore, proper regulation of Myc is very important to ensure normal development. Regulation of Myc occurs by several context specific mechanisms. One such mechanism is the negative feedback autoregulation of Myc and this mechanism is lost in all tumorigenic cell lines. Like its mammalian homolog, the Drosophila Myc (dMyc) undergoes autoregulation in the presence of an ectopic myc gene leading to a Myc null phenotype. Polycomb (Pc), a chromatin binding repressor is required for Myc autoregulation. Upon Pc knockdown, levels of Su(z)2, a Pc group related protein increase significantly, suggesting that Pc represses Su(z)2. We show here that ectopic Su(z)2 can interfere with Myc autorepression and restore endogenous Myc levels as well as rescue larval lethality caused due to Myc autorepression. Su(z)2 does not however, affect general repression by Myc suggesting that repression of myc locus occurs by a different mechanism. During this study we observed that Myc protein forms distinct puncta in certain tissues. Upon investigating we found that these Myc "spots" localize to sub-nuclear organelles known as Histone Locus Body (HLB). HLBs are histone pre-mRNA processing centers formed at histone gene locus. We show here that Myc localizes to the HLBs only during the S phase. Since hisones are transcribed only during S phase we hypothesize that Myc aids in histone transcription, a novel role for Myc
Goodliffe, Dr. Julie
Parrow, Dr. MatthewRichardson, Dr. ChristineMukherjee, Dr. PinkuBender, Dr. John
Thesis (Ph.D.)--University of North Carolina at Charlotte, 2012.
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