Unexpected link between MAX and meiotic onset
Unexpected link between MAX and meiotic onset
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MAX 和减数分裂开始之间的意外联系
DOI：
10.1080/15384101.2016.1194137
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发表时间：
2016
期刊：
影响因子：
4.3
通讯作者：
A.
中科院分区：
文献类型：
--
作者：
Okuda;A.;Suzuki;A.
生殖细胞是一种独特的程序化细胞谱系，可以将遗传和表观遗传信息传递给后代。与体细胞类似，生殖细胞经历长时间的有丝分裂以增加它们的数量。然而，生殖细胞将其细胞分裂模式从有丝分裂转换到减数分裂，在适当的时间点转换为单倍体细胞；雌性生殖细胞在怀孕中期在生殖器脊经历减数分裂，而雄性生殖细胞在哺乳动物出生后在睾丸启动这种转换。虽然已知维甲酸在这一转变中起着至关重要的作用，但调控这一转变的分子机制仍很不清楚。然而，我们最近的研究发现，MAX是减数分裂的负调控因子，分别抑制胚胎干细胞(ESCs)和精原干细胞(SSCs)的异位和早熟减数分裂开始。1在得出这一结论之前，我们首先通过对联会复合体的主要成分SYCP3的免疫细胞化学分析，证明了在ESCs中，MAX表达消融不仅激活了减数分裂相关基因的表达，而且还诱导了类似于细线期和合线期生殖细胞的细胞学变化。2我们还表明这些细胞学变化依赖于维甲酸-STRA8轴，强调这些变化真实地概括了真正的减数分裂过程。然而，有趣的是，我们发现，MAX表达抑制的ESCs似乎直接转化为减数分裂样细胞，而不需要经过原始生殖细胞状态。随后，我们证明了在雄性和雌性生殖细胞减数分裂早期，MAX基因的表达水平都出现了短暂但显著的下降，这意味着MAX表达水平的下调是减数分裂所必需的生理步骤。最后，我们发现在SSCs中强制降低MAX的表达比在ESCs中观察到的更有效地诱导减数分裂进入。MAX通常被认为是MYC的一种专职伙伴蛋白，具有转录因子的功能。3事实上，MYC本身几乎没有固有的DNA结合活性，而Max赋予MYC这种活性。MYC/MAX转录
Germ cells are uniquely programmed cell lineage that can transfer genetic and epigenetic information to subsequent generations. Similar to somatic cells, germ cells undergo mitosis for substantial durations to increase their numbers. However, germ cells switch their mode of cell division from mitosis to meiosis to convert to haploid cells at appropriate time points; female germ cells undergo meiosis in the genital ridge at midgestation, but male germ cells initiate this switch after birth in the testes of mammals. Although it is known that retinoic acid is crucially involved in this transition, the molecular mechanisms governing the switch remain largely obscure. However, our recent study revealed MAX as a negative regulator of meiosis, suppressing ectopic and precocious meiotic onset in embryonic stem cells (ESCs) and spermatogonial stem cells (SSCs), respectively. 1Before reaching this conclusion, we first demonstrated that Max expression ablation in ESCs not only activates expression of meiosis-related genes, but also induces cytological changes reminiscent of germ cells at leptotene and zygotene stages of meiosis by immunocytochemical analysis of SYCP3, a major component of the synaptonemal complex. 2 We also showed that these cytological changes are dependent on the retinoic acid-STRA8 axis, underscoring that these changes faithfully recapitulate bona fide meiotic processes. However, intriguingly, we found that Max expression-ablated ESCs appear to directly convert to meiosis-like cells without passing through the primordial germ cell state. Subsequently, we demonstrated that the Max gene shows a transient but significant decline in its expression level during the early stage of meiosis in both male and female germ cells, implying that downregulation of Max expression levels is a physiologically required step for meiosis. Finally, we found that forced reduction of Max expression in SSCs induces meiotic entry with much greater efficiency compared with that observed in ESCs. MAX is generally known as an obligated partner protein of MYC that functions as a transcription factor. 3 Indeed, MYC by itself has almost no intrinsic DNA-binding activity, and MAX confers that activity on MYC. MYC/MAX transcription
影响因子：
16
作者：
Trojer P;Cao AR;Gao Z;Li Y;Zhang J;Xu X;Li G;Losson R;Erdjument-Bromage H;Tempst P;Farnham PJ;Reinberg D
通讯作者：
Reinberg D
影响因子：
56.9
作者：
BLACKWOOD, EM;EISENMAN, RN
通讯作者：
EISENMAN, RN