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      Wake-up-call, a lin-52 paralogue, and Always early, a lin-9 homologue physically interact, but have opposing functions in regulating testis-specific gene expression

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          A conserved multi-subunit complex (MybMuvB, MMB), regulates transcriptional activity of many different target genes in Drosophila somatic cells. A paralogous complex, tMAC, controls expression of at least 1500 genes in the male germline, and is essential for sperm production. The roles of specific subunits of tMAC, MMB or orthologous complexes in regulating target gene expression are not understood. MMB and orthologous complexes have Lin-52 as a subunit, but Lin-52 did not co-purify with tMAC. We identified wake-up-call ( wuc), a lin-52 paralogue, via a physical interaction with the tMAC lin-9-related subunit Aly, and find that Wuc co-localises with known tMAC subunits. We show that wuc, like aly, is required for spermatogenesis. However, despite phenotypic similarities, the role of wuc is very different from that of previously characterised tMAC mutants. Unlike aly, loss of wuc results in only relatively mild defects in testis-specific gene expression. Strikingly, wuc loss of function partially rescues expression of target genes in aly mutant testes. We propose that wuc represses testis-specific gene expression, that this repression is counteracted by aly, and that aly and a testis-specific TF IID complex work together to promote high transcriptional activity of spermiogenic genes specifically in primary spermatocytes.

          Research highlights

          ► wake-up-call ( wuc), a paralogue of lin-52 functions in the Drosophila male germline. ► Wuc protein physically interacts with the lin-9 homologue, Aly. ► wuc is essential for male fertility. ► wuc loss of function causes defects in gene expression in testes. ► Transcription of aly target genes in testes can be rescued by wuc loss of function.

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          Most cited references 41

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          A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila.

          Forward genetic screens in model organisms have provided important insights into numerous aspects of development, physiology and pathology. With the availability of complete genome sequences and the introduction of RNA-mediated gene interference (RNAi), systematic reverse genetic screens are now also possible. Until now, such genome-wide RNAi screens have mostly been restricted to cultured cells and ubiquitous gene inactivation in Caenorhabditis elegans. This powerful approach has not yet been applied in a tissue-specific manner. Here we report the generation and validation of a genome-wide library of Drosophila melanogaster RNAi transgenes, enabling the conditional inactivation of gene function in specific tissues of the intact organism. Our RNAi transgenes consist of short gene fragments cloned as inverted repeats and expressed using the binary GAL4/UAS system. We generated 22,270 transgenic lines, covering 88% of the predicted protein-coding genes in the Drosophila genome. Molecular and phenotypic assays indicate that the majority of these transgenes are functional. Our transgenic RNAi library thus opens up the prospect of systematically analysing gene functions in any tissue and at any stage of the Drosophila lifespan.
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            Using FlyAtlas to identify better Drosophila melanogaster models of human disease.

            FlyAtlas, a new online resource, provides the most comprehensive view yet of expression in multiple tissues of Drosophila melanogaster. Meta-analysis of the data shows that a significant fraction of the genome is expressed with great tissue specificity in the adult, demonstrating the need for the functional genomic community to embrace a wide range of functional phenotypes. Well-known developmental genes are often reused in surprising tissues in the adult, suggesting new functions. The homologs of many human genetic disease loci show selective expression in the Drosophila tissues analogous to the affected human tissues, providing a useful filter for potential candidate genes. Additionally, the contributions of each tissue to the whole-fly array signal can be calculated, demonstrating the limitations of whole-organism approaches to functional genomics and allowing modeling of a simple tissue fractionation procedure that should improve detection of weak or tissue-specific signals.
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              Is Open Access

              FlyBase: enhancing Drosophila Gene Ontology annotations

              FlyBase ( is a database of Drosophila genetic and genomic information. Gene Ontology (GO) terms are used to describe three attributes of wild-type gene products: their molecular function, the biological processes in which they play a role, and their subcellular location. This article describes recent changes to the FlyBase GO annotation strategy that are improving the quality of the GO annotation data. Many of these changes stem from our participation in the GO Reference Genome Annotation Project—a multi-database collaboration producing comprehensive GO annotation sets for 12 diverse species.

                Author and article information

                Dev Biol
                Dev. Biol
                Developmental Biology
                15 July 2011
                15 July 2011
                : 355
                : 2-2
                : 381-393
                [a ]Department of Zoology, University of Oxford, South Parks Rd, Oxford, OX1 3PS, UK
                [b ]School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3AX, UK
                Author notes
                [* ]Corresponding author. Fax: + 44 29 20874116. white-cooperh@

                Present address: Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia.

                © 2011 Elsevier Inc.

                This document may be redistributed and reused, subject to certain conditions.

                Genomes & Developmental Control

                Developmental biology

                drosophila, testis gene expression, male fertility, transcription


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