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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

机译:唤醒呼叫是lin-52的旁系同源物,而永远是早期的lin-9同源物在物理上相互作用,但是在调节睾丸特异性基因表达方面具有相反的功能

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摘要

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 TFIID complex work together to promote high transcriptional activity of spermiogenic genes specifically in primary spermatocytes.
机译:保守的多亚基复合物(MybMuvB,MMB)调节果蝇体细胞中许多不同靶基因的转录活性。旁系复合体tMAC控制雄性种系中至少1500个基因的表达,并且对精子产生至关重要。 tMAC,MMB或直系同源复合物的特定亚基在调节靶基因表达中的作用尚不清楚。 MMB和直系同源复合体具有Lin-52作为亚基,但Lin-52并未与tMAC共纯化。我们通过与tMAC lin-9相关的亚基Aly的物理相互作用,鉴定了lin-52旁听的唤醒呼叫(wuc),并发现Wuc与已知的tMAC亚基共定位。我们显示,与aly一样,wuc是精子发生所必需的。然而,尽管有表型上的相似性,但wuc的作用与以前表征的tMAC突变体却有很大不同。与aly不同,wuc的损失仅导致睾丸特异性基因表达中相对温和的缺陷。令人惊讶的是,wuc功能丧失部分拯救了突变突变型睾丸中靶基因的表达。我们提议,wuc抑制睾丸特异性基因表达,这种抑制作用被aly抵消,而aly和睾丸特异性TFIID复合体共同作用以促进原发性精子细胞中的生精基因的高转录活性。

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