Promotion of oogenesis and embryogenesis in the C. elegans gonad by EFL-1/DPL-1 (E2F) does not require LIN-35 (pRB).
Promotion of oogenesis and embryogenesis in the C. elegans gonad by EFL-1/DPL-1 (E2F) does not require LIN-35 (pRB).
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DOI：
10.1242/dev.02490
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发表时间：
2006-08-01
期刊：
影响因子：
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通讯作者：
Reinke, Valerie
中科院分区：
文献类型：
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作者：
Chi, Woo;Reinke, Valerie
在秀丽隐杆线虫中，EFL-1（E2 F）、DPL-1（DP）和LIN-35（pRb）在体细胞组织中协同作用，可能通过抑制靶基因的表达来抑制异位细胞分裂。EFL-1、DPL-1和LIN-35也存在于生殖系中，但并不总是一起起作用。efl-1或dpl-1的功能缺失突变导致卵子发生缺陷，导致不育，而lin-35突变体可育，但窝数减少。基于微阵列的表达谱的切割性腺efl-1，dpl-1和lin-35突变体揭示，EFL-1和DPL-1促进表达的一个广泛重叠的一组靶基因，与预期的这两个蛋白质作为异源二聚体的功能。许多这些靶基因的上游调控区具有典型的E2 F结合位点，这表明EFL-1/DPL-1对它们的调控是直接的。许多EFL-1/DPL-1应答基因编码卵子发生和早期胚胎发生所需的蛋白质，而不是细胞周期组分。相比之下，LIN-35似乎主要作为生殖系中基因表达的阻遏物起作用，并且其作用的基因大部分不同于由EFL-1和/或DPL-1调节的基因。因此，在体内，C. elegans E2 F通过激活不需要LIN-35的组织特异性转录程序直接促进卵子发生和胚胎发生。
In Caenorhabditis elegans, EFL-1 (E2F), DPL-1 (DP) and LIN-35 (pRb) act coordinately in somatic tissues to inhibit ectopic cell division, probably by repressing the expression of target genes. EFL-1, DPL-1 and LIN-35 are also present in the germline, but do not always act together. Strong loss-of-function mutations in either efl-1 or dpl-1 cause defects in oogenesis that result in sterility, while lin-35 mutants are fertile with reduced broods. Microarray-based expression profiling of dissected gonads from efl-1, dpl-1 and lin-35 mutants reveals that EFL-1 and DPL-1 promote expression of an extensively overlapping set of target genes, consistent with the expectation that these two proteins function as a heterodimer. Regulatory regions upstream of many of these target genes have a canonical E2F-binding site, suggesting that their regulation by EFL-1/DPL-1 is direct. Many EFL-1/DPL-1 responsive genes encode proteins required for oogenesis and early embryogenesis, rather than cell cycle components. By contrast, LIN-35 appears to function primarily as a repressor of gene expression in the germline, and the genes that it acts on are for the most part distinct from those regulated by EFL-1 and/or DPL-1. Thus, in vivo, C. elegans E2F directly promotes oogenesis and embryogenesis through the activation of a tissue-specific transcriptional program that does not require LIN-35.