Biomedical Sciences Department and Program in Neuroscience, Florida State University, College of Medicine, Tallahassee, FL 32303, USA.
BMC Genomics. 2013 Sep 27;14:659. doi: 10.1186/1471-2164-14-659.
Drosophila melanogaster adult males perform an elaborate courtship ritual to entice females to mate. fruitless (fru), a gene that is one of the key regulators of male courtship behavior, encodes multiple male-specific isoforms (Fru(M)). These isoforms vary in their carboxy-terminal zinc finger domains, which are predicted to facilitate DNA binding.
By over-expressing individual Fru(M) isoforms in fru-expressing neurons in either males or females and assaying the global transcriptional response by RNA-sequencing, we show that three Fru(M) isoforms have different regulatory activities that depend on the sex of the fly. We identified several sets of genes regulated downstream of Fru(M) isoforms, including many annotated with neuronal functions. By determining the binding sites of individual Fru(M) isoforms using SELEX we demonstrate that the distinct zinc finger domain of each Fru(M) isoforms confers different DNA binding specificities. A genome-wide search for these binding site sequences finds that the gene sets identified as induced by over-expression of Fru(M) isoforms in males are enriched for genes that contain the binding sites. An analysis of the chromosomal distribution of genes downstream of Fru(M) shows that those that are induced and repressed in males are highly enriched and depleted on the X chromosome, respectively.
This study elucidates the different regulatory and DNA binding activities of three Fru(M) isoforms on a genome-wide scale and identifies genes regulated by these isoforms. These results add to our understanding of sex chromosome biology and further support the hypothesis that in some cell-types genes with male-biased expression are enriched on the X chromosome.
黑腹果蝇雄成虫会进行复杂的求爱仪式，以吸引雌性交配。fru 基因是调控雄虫求爱行为的关键基因之一，它编码多种雄性特异性的异构体（Fru(M)）。这些异构体在其羧基末端锌指结构域存在差异，这些结构域被预测有助于 DNA 结合。
通过在雄虫或雌虫中fru 表达神经元中过表达单个 Fru(M)异构体，并通过 RNA-seq 检测全局转录反应，我们发现三个 Fru(M)异构体具有不同的调节活性，这取决于果蝇的性别。我们鉴定了几个受 Fru(M)异构体下游调控的基因集，其中包括许多注释为神经元功能的基因。通过使用 SELEX 确定单个 Fru(M)异构体的结合位点，我们证明了每个 Fru(M)异构体独特的锌指结构域赋予了不同的 DNA 结合特异性。对这些结合位点序列的全基因组搜索发现，通过过表达 Fru(M)异构体在雄虫中诱导的基因集富含含有结合位点的基因。对 Fru(M)下游基因的染色体分布分析表明，在雄虫中被诱导和抑制的基因分别在 X 染色体上高度富集和缺失。
本研究阐明了三个 Fru(M)异构体在全基因组范围内的不同调节和 DNA 结合活性，并鉴定了受这些异构体调控的基因。这些结果增加了我们对性染色体生物学的理解，并进一步支持了这样的假设，即在某些细胞类型中，雄性偏表达的基因在 X 染色体上富集。
