The role of ZFH-2 in apoptosis and gene insulation

Date

2009

Authors

Reddy, Guntur Ananya

Journal Title

Journal ISSN

Volume Title

Publisher

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.

Description

This item is available only to currently enrolled UTSA students, faculty or staff. To download, navigate to Log In in the top right-hand corner of this screen, then select Log in with my UTSA ID.

Keywords

APOPTOSIS, GENE INSULATION, NB7-3, OOGENESIS, SPRINGER, ZFH-2

Citation

Department

Integrative Biology