The bromodomain-containing protein tBRD-1 is specifically expressed in spermatocytes and is essential for male fertility.
The bromodomain-containing protein tBRD-1 is specifically expressed in spermatocytes and is essential for male fertility.
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DOI：
10.1242/bio.20121255
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发表时间：
2012-06-15
期刊：
影响因子：
2.4
通讯作者：
Rathke C
中科院分区：
文献类型：
--
作者：
Leser K;Awe S;Barckmann B;Renkawitz-Pohl R;Rathke C
通过保守的细胞分化过程，精子发生导致单倍体精子的形成，以实现成功繁殖。在果蝇和哺乳动物中，减数分裂后精细胞分化取决于几种翻译抑制和储存的 mRNA，这些 mRNA 通常通过细胞类型特异性转录程序仅在睾丸中表达。在果蝇中，减数分裂后染色质重组所需的蛋白质 mRNA（如 ProtB 和 Mst77F）在减数分裂精母细胞中转录，并受到数天的翻译抑制。许多这些翻译抑制 mRNA 的转录依赖于 TATA 盒结合蛋白相关因子 (tTAF) 的睾丸特异性同源物。在这里，我们鉴定了睾丸特异性溴结构域蛋白 tBRD-1，它仅在初级精母细胞中表达。溴结构域蛋白能够识别并结合乙酰化组蛋白和非组蛋白。我们生成了 tBRD-1 突变果蝇，并观察到 tBRD-1 的功能是雄性生育能力所必需的。 tBRD-1 与 tTAF、TAF1 和 Polycomb 部分共定位于精母细胞核仁内的 Fibrillarin 缺陷区域。 tBRD-1 的核仁定位取决于 tTAF 功能，但反之则不然。此外，我们还可以证明异位表达的 tBRD-1-eGFP 能够与多线染色体的带间结合。通过对培养的睾丸进行抑制剂处理，我们观察到 tBRD-1 的亚细胞定位可能取决于原代精母细胞的乙酰化状态。
By a conserved cellular differentiation process, spermatogenesis leads to formation of haploid sperm for successful reproduction. In Drosophila and in mammals, post-meiotic spermatid differentiation depends on several translationally repressed and stored mRNAs that are often expressed exclusively in the testis through a cell type specific transcriptional program. In Drosophila, the mRNAs of proteins required for post-meiotic chromatin reorganisation, like ProtB and Mst77F, are transcribed in meiotic spermatocytes and subjected to translational repression for days. Transcription of many of these translationally repressed mRNAs depends on testis-specific homologs of TATA box binding protein-associated factors (tTAFs). Here, we identified the testis-specific bromodomain protein, tBRD-1, that is only expressed in primary spermatocytes. Bromodomain proteins are able to recognise and bind acetylated histones and non-histone proteins. We generated tbrd-1 mutant flies and observed that function of tBRD-1 is required for male fertility. tBRD-1 partially colocalised with tTAFs, TAF1 and Polycomb to a Fibrillarin-deficient region within the spermatocyte nucleolus. The nucleolar localisation of tBRD-1 depended on tTAF function but not the other way round. Further, we could show that ectopically expressed tBRD-1-eGFP is able to bind to the interbands of polytene chromosomes. By inhibitor treatment of cultured testis we observed that sub-cellular localisation of tBRD-1 may depend on the acetylation status of primary spermatocytes.
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