The role of ZFH-2 in apoptosis and gene insulation

Date
2009
Authors
Reddy, Guntur Ananya
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Abstract

This thesis examines the function of a Drosophila transcription factor, Zinc-Finger Homeodomain-2 (ZFH-2). We provide evidence that suggests ZFH-2 can induce apoptosis in two different tissues, the central nervous system and the leg joints. In two separate neuronal lineages, a zfh-2 loss-of-function allele can rescue cells that normally undergo apoptosis. In contrast ectopic expression of zfh-2 in these same lineages reduces the number of detectable cells that normally survive development. In the leg we show that ZFH-2 co-localizes with apoptotic cells in the joints and that a zfh-2 mutation disrupt joint development. We present a model where ZFH-2 works in conjunction with NOTCH signaling to induce apoptosis.

We also examine the regulation of zfh-2 in the central nervous system and find that increased levels of the transcription factor HUNCHBACK leads to a decrease in ZFH-2 levels and rescue of apoptotic cells. In contrast, decreased levels of the ubiquitin ligase ABBA, leads to misexpression of ZFH-2 and increased apoptosis. These results suggest that HUNCHBACK regulates zfh-2 gene expression and ABBA regulates proteolysis of ZFH-2 protein.

In addition, we identify ZFH-2 as an insulator binding protein. Using a previously identified Springer element that insulates the daughterless promoter, we show that the binding of ZFH-2 to this Springer element is necessary for the insulation effect and that loss of ZFH-2 function prevents insulation. We confirm that the ovary has endogenous ZFH-2 expression, and that zfh-2 mutant ovarioles have defects that include a reduction in number and a fusion of egg chambers.

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Keywords
APOPTOSIS, GENE INSULATION, NB7-3, OOGENESIS, SPRINGER, ZFH-2
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Department
Integrative Biology