Genome-wide analysis of gene regulation mechanisms during Drosophila spermatogenesis.

Genome-wide analysis of gene regulation mechanisms during Drosophila spermatogenesis.
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DOI:
10.1186/s13072-018-0183-3
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发表时间:
2018-04-02
影响因子:
3.9
通讯作者:
Belyakin SN
Belyakin SN
中科院分区:
生物学2区
文献类型:
--
作者:
Laktionov PP;Maksimov DA;Romanov SE;Antoshina PA;Posukh OV;White-Cooper H;Koryakov DE;Belyakin SN

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在果蝇精子发生过程中,睾丸特异的减数分裂抑制复合体(TMAC)和睾丸特异的TBP相关因子(TTAF)有助于激活数百个减数分裂和精子发生所需的基因。有趣的是,TMAC与广泛表达的复合体Myb-MuvB(MMB)/Dream相似,Mip40蛋白由两个复合体共享。TMAC在精母细胞中作为基因激活剂,而MMB/DREAM被证明在许多类型的细胞中抑制基因活性。我们的研究解决了TMAC、tTAF和MMB/DREAM之间在精子发生过程中的复杂相互作用。我们使用细胞类型特异性的DamID在雄性生殖细胞中建立了Cookie Monster(TMAC)、Cannonball(TTAF)和Mip40(MMB/DREAM和TMAC)蛋白的DNA结合图谱。结合整个转录组分析,我们表征了这些蛋白的调控作用,并确定了它们的基因靶标。这一分析表明,tTAFs复合体参与了Achi、Vis和Topi减数分裂停滞基因的激活,这意味着tTAFs可能间接参与了对Achi、Vis和Topi靶标的调控。为了了解TMAC和MMB/DREAM之间的关系,我们对表现减数分裂停止表型的tTAF和TMAC缺陷突变体进行了Mip40DamID检测。Mip40的DAMID谱在精子发生的各个阶段都是高度动态的,并且在精母细胞中显示出对TMAC的强烈依赖。对我们数据的综合分析表明,MMB/DREAM抑制在精子发生中不表达的基因,而TMAC招募Mip40用于后续精母细胞中的基因激活。已发现的相互依赖关系使我们能够为TMAC和tTAFs在果蝇精子发生中的作用制定一个新的模型,展示组织特异性基因是如何受到调控的。本文的在线版本(10.1186/s13072-0180183-3)包含向授权用户提供的补充材料。
During Drosophila spermatogenesis, testis-specific meiotic arrest complex (tMAC) and testis-specific TBP-associated factors (tTAF) contribute to activation of hundreds of genes required for meiosis and spermiogenesis. Intriguingly, tMAC is paralogous to the broadly expressed complex Myb-MuvB (MMB)/dREAM and Mip40 protein is shared by both complexes. tMAC acts as a gene activator in spermatocytes, while MMB/dREAM was shown to repress gene activity in many cell types. Our study addresses the intricate interplay between tMAC, tTAF, and MMB/dREAM during spermatogenesis. We used cell type-specific DamID to build the DNA-binding profiles of Cookie monster (tMAC), Cannonball (tTAF), and Mip40 (MMB/dREAM and tMAC) proteins in male germline cells. Incorporating the whole transcriptome analysis, we characterized the regulatory effects of these proteins and identified their gene targets. This analysis revealed that tTAFs complex is involved in activation of achi, vis, and topi meiosis arrest genes, implying that tTAFs may indirectly contribute to the regulation of Achi, Vis, and Topi targets. To understand the relationship between tMAC and MMB/dREAM, we performed Mip40 DamID in tTAF- and tMAC-deficient mutants demonstrating meiosis arrest phenotype. DamID profiles of Mip40 were highly dynamic across the stages of spermatogenesis and demonstrated a strong dependence on tMAC in spermatocytes. Integrative analysis of our data indicated that MMB/dREAM represses genes that are not expressed in spermatogenesis, whereas tMAC recruits Mip40 for subsequent gene activation in spermatocytes. Discovered interdependencies allow to formulate a renewed model for tMAC and tTAFs action in Drosophila spermatogenesis demonstrating how tissue-specific genes are regulated. The online version of this article (10.1186/s13072-018-0183-3) contains supplementary material, which is available to authorized users.
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