PgmNr D1462: Transcriptional regulation by Drosophila Suppressor of Hairy-wing: Investigating contributions of a newly discovered interacting protein HIPP1.

Authors:
Steve Glenn; Pamela Geyer


Institutes
University of Iowa, Iowa City, IA.


Keyword: repressors/corepressors

Abstract:

Transcription is regulated by three classes of DNA regulatory elements: enhancers, silencers and insulators. Transcription factors bind these elements to coordinate gene expression across cell types and developmental stages. Most metazoan transcription factors carry Zinc finger (ZF) DNA binding domains, often with five or more ZFs. Many polydactyl transcription factors have distinct regulatory functions at different endogenous binding sites. How these activities are regulated is unclear.  To better understand how a single transcription factor establishes enhancer, silencer and insulator functions, we study the Drosophila multi-functional twelve ZF insulator protein Suppressor of Hairy-wing [Su(Hw)]. Su(Hw) functions primarily as a repressor, and this activity is required in the ovary for female fertility. Su(Hw) is also important for male fertility through unknown mechanisms. We hypothesize that the diversity of Su(Hw) regulatory functions depends upon recruitment of partner proteins. Recently a novel Su(Hw) interactor was identified, called HP1 and insulator partner protein 1 (HIPP1). We find that HIPP1 is the major Su(Hw) interacting protein, localizing to more than 80% of Su(Hw) sites.  HIPP1 is homologous to the vertebrate Chromodomain on Y (CDY), a transcriptional repressor that is required for spermatogenesis in mouse.  These data suggest that HIPP1 may mediate Su(Hw) repressor function.   To test this hypothesis, we undertook a genetic approach using genome editing to generate numerous HIPP1 deletion mutants. We are currently using these mutants to determine the role of HIPP1 in Su(Hw) function, as well as defining its role in heterochromatin stability and function.



Flybase Genetic Index:
1. FlyBase gene symbol: su(Hw); FBgn: FBgn0003567
2. FlyBase gene symbol: HIPP1; FBgn: FBgn0037027