Regulation of Myc and its Localization to Histone Locus Body in Drosophila

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Khan, A. (2012). Regulation of Myc and its Localization to Histone Locus Body in Drosophila. Unc Charlotte Electronic Theses And Dissertations.
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Abstract

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

Details
Author

Khan, Abid

Title

Regulation of Myc and its Localization to Histone Locus Body in Drosophila

Physical Description

1 online resource (90 pages) : PDF

Date

2012

Degree Granting Institution

University of North Carolina at Charlotte

Abstract

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

Genre

doctoral dissertations

Subjects--Topics

Molecular biology
Biology
Developmental biology

Degree

Ph.D.

Keywords

Autoregulation
Cajal Bodies
HLB
MYC
Su(z)2

Subject Area

Biology

Advisor(s)

Goodliffe, Dr. Julie

Committee Members

Parrow, Dr. Matthew
Richardson, Dr. Christine
Mukherjee, Dr. Pinku
Bender, Dr. John

Degree Note

Thesis (Ph.D.)--University of North Carolina at Charlotte, 2012.

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Rights Holder Information

Copyright is held by the author unless otherwise indicated.

Identifier

Khan_uncc_0694D_10347

Permalink

http://hdl.handle.net/20.500.13093/etd:892