Question

·生物专业英语翻译？急！！！（不要软件和在线翻译！）

Here, we analyze the molecular mechanisms that determine the temporal patterning of a subset of MyoD regulated genes. We show that Mef2 expression and p38 activity increase in response to MyoD. Binding of MyoD and Mef2 proteins at late-stage genes is temporally delayed until there is sufficient activity of p38. Transcription of this subset of promoters is further delayed until the Mef2D isoform joins the complex and then recruits Pol II. The expression of this subset of normally lateexpressed genes can be shifted to an earlier time relative to other MyoD targets by the precocious expression of Mef2D and an active p38 kinase. This demonstrates that a MyoD-generated feed-forward regulatory circuit, wherein factors induced by MyoD feed-forward to regulate MyoD activity at subsequent target genes, acts to temporally pattern the relative timing of gene expression during skeletal myogenesis.

Results and Discussion
p38 and Mef2D regulate the timing of a subset of genes during myogenesis

Our previously published microarray analysis using MyoD-ER showed early-stage induction of Mef2 isoforms and other factors that participate in the myogenic program (Bergstrom et al. 2002), consistent with numerous other studies in myoblast cell lines. Northern and Western analyses confirm that expression of both Mef2A and Mef2D increases in response to MyoD-ER (Fig. 1B). Retarded gel mobility of these proteins at later time points indicates increased phosphorylation, and treatment of cells with the p38 inhibitor SB203580 prevents the appearance of hyperphosphorylated Mef2, demonstrating a MyoD-induced activation of p38 and subsequent p38-dependent phosphorylation of Mef2A and Mef2D. In addition, in vitro kinase assays showed that both Mef2A and Mef2D are directly phosphorylated by p38 (data not shown).

Our prior microarray studies demonstrated that inhibition of p38 resulted in decreased expression of a subset of MyoD target genes. This effect was selective for genes normally expressed during the second day of the myogenic program, suggesting a potential role for p38 in regulating the timing of gene activation. To test this hypothesis, we assessed MyoD-induced gene expression in cells with precociously elevated p38 activity, achieved by the expression of MKK6E, an activated allele of the p38 upstream regulator (Han et al. 1996). Array analysis of genes expressed at 24 h following MyoD-ER induction identified a subset of genes that were more highly expressed in the presence of active p38 (fold change > 2×and q < 0.10; Supplementary Table 1). Compared with our previous study, the ability of MyoD to induce this set of genes was also inhibited by SB203580 (p = 0.003), indicating that the level of p38 activity regulates MyoDmediated expression at this subset of promoters.

Answer 1

在这里，我们分析的分子机制，确定颞图案化的一个子集MyoD的调节基因。我们证明了mef2表达和p38活性增加，反应MyoD的。装订MyoD的和mef2蛋白质在晚期基因是暂时性的延迟，直到有足够的活性p38的。转录本的子推动者是一拖再拖，直到mef2d亚型加入复杂的，然后在新兵油料二。表明此子通常lateexpressed基因可转移到一个较早的时间相对于其他MyoD的目标早熟表达mef2d和一个积极p38激酶。这说明MyoD的产生前馈调节电路，其中因素诱导MyoD的前馈调节MyoD的活性，在随后的靶基因，行为，以暂时性的格局相对时机基因表达在骨骼肌肉发生。

结果与讨论
p38和mef2d调控时机的一个子基因在肌肉

我们先前发表的微阵列分析中的应用MyoD的儿表明前期诱导mef2亚型和其他的因素，参加在生肌计划（安大略等人2002年） ，与许多其他研究，在成肌细胞系。北部和西部的分析证实，表达双方的mef2a和mef2d增加响应MyoD的儿（图1B ）条。迟钝凝胶的流动性，这些蛋白质在稍后的时间点，显示上升的磷酸化，以及治疗的细胞与P38的抑制剂SB203580防止出现hyperphosphorylated mef2 ，表现出一个MyoD的诱导活化的p38和随后的p38的依赖性磷酸化mef2a和mef2d 。此外，在体外激酶检测显示，无论mef2a和mef2d直接磷酸化P38的（数据未显示） 。

我们事先微阵列研究表明，抑制P38的结果是减少了表达的一个子集MyoD的靶基因。这种作用是有选择性的基因表达，通常在第二天的肌性纲领，建议一个潜在的作用，为p38的调节时机的基因活化。为验证这一假说，我们评估MyoD的诱导基因表达细胞precociously高架P38的活动，所取得的表达mkk6e ，活化等位基因的P38的上游调节器（韩等， 1996年） 。阵列分析基因表达，在24小时以下MyoD的儿感应确定的一个子集的基因，更高效表达，在存在活跃的P38的（褶皱变化> 2 ×和Q < 0.10 ;补充表1 ） 。相比，与我们先前的研究中，有能力的MyoD的诱使这一套基因也能抑制由SB203580干预性（ P = 0.003 ） ，显示水平p38的活性调节myodmediated表达，在此子的推动者。

Answer 2

在这里，我们分析了确定temporal patterning of a subset MyoD的调节基因的分子机制。我们证明了mef2表达和p38活化增强MyoD的作用。直到有足够的活化p38，在晚期基因中结合的MyoD和mef2蛋白才活化。直到mef2d亚型加入复合体，并招募Pol II启动子才开始转录。
haoxiangbutong!