In Silico Prediction of Transcription Factor Collaborations Underlying Phenotypic Sexual Dimorphism in Zebrafish (Danio rerio).

Shahrbanou Hosseini,Jens Tetens,Armin Otto Schmitt,Henner Simianer,Mehmet Gültas,Ahmad Reza Sharifi,Bertram Brenig

doi:10.3390/genes12060873

Abstract

The transcriptional regulation of gene expression in higher organisms is essential for different cellular and biological processes. These processes are controlled by transcription factors and their combinatorial interplay, which are crucial for complex genetic programs and transcriptional machinery. The regulation of sex-biased gene expression plays a major role in phenotypic sexual dimorphism in many species, causing dimorphic gene expression patterns between two different sexes. The role of transcription factor (TF) in gene regulatory mechanisms so far has not been studied for sex determination and sex-associated colour patterning in zebrafish with respect to phenotypic sexual dimorphism. To address this open biological issue, we applied bioinformatics approaches for identifying the predicted TF pairs based on their binding sites for sex and colour genes in zebrafish. In this study, we identified 25 (e.g., STAT6-GATA4; JUN-GATA4; SOX9-JUN) and 14 (e.g., IRF-STAT6; SOX9-JUN; STAT6-GATA4) potentially cooperating TFs based on their binding patterns in promoter regions for sex determination and colour pattern genes in zebrafish, respectively. The comparison between identified TFs for sex and colour genes revealed several predicted TF pairs (e.g., STAT6-GATA4; JUN-SOX9) are common for both phenotypes, which may play a pivotal role in phenotypic sexual dimorphism in zebrafish.

Highlights

Transcription factors (TFs) are a large class of DNA-binding proteins that play a central role in controlling the rate of transcription
To gain more insights into the cooperation of these TF pairs for each phenotype, we created a network for sex determination (Figure 2) and colour pattern (Figure 3) genes, which were compared to identify the common TF pairs for both phenotypes (Figure 4)
Focusing on the three top highly connected TF pairs in this network, we identified STAT6, interferon-regulatory factor (IRF), and JUN as hubs (Figure 3)

Summary

Introduction

Transcription factors (TFs) are a large class of DNA-binding proteins that play a central role in controlling the rate of transcription They bind to specific DNA sequence motifs, cis-regulatory elements, in promoter and/or enhancer/silencer regions to regulate gene expression [1,2]. Sex determination is a complex biological process that directs the undifferentiated bipotent gonad to develop into either a testis or an ovary [6] This mechanism leads to a stable sexual fate in most animal classes, whereas in some animal classes such as teleost fish species, sex can be reversed during the critical developmental period [7]. The alternative genetic networks, including ovarian-determining genes such as RSPO1, Wnt4/β-catenin, and Foxl regulate female gonadal development [14] In this process, gonadal hormones contribute to sex differences by influencing gene expression. A number of TFs such as SRY, SOX9, and NR5A1 are known to regulate the sex-determining pathway in mammals resulting in sexual differentiation [15]

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