myoD表达时间对肌纤维数量的影响及其在猪品种间表达时间差异的分子机制

在肌肉特异基因转录调控中，MyoD起着总开关的作用。但以往研究主要集中于它的表达（量）对成肌细胞分化的调控，我们新近观察到受精后21天时，五指山小型猪已有myoD的表达，蓝塘猪仅有少量表达，而瘦肉型长白猪几乎无表达，提示myoD的起始表达时间可能决定了成肌细胞增殖与分化时间，进而决定肌纤维数量并最终影响产肉量。不仅如此，受精21天后，促进转录的H3K4me3在五指山猪的表达量比抑制转录的H3K27me3高，有助于促进分化；而在长白猪中两者平衡表达有助于成肌细胞增殖，这与预期完全相符，为此，本课题拟通过构建myoD可诱导表达并同时敲除myf5的小鼠模型证实是否可通过控制myoD的表达时间来影响肌纤维数量，并通过Chip等实验阐明myoD在产肉量不同猪种中起始表达时间差异的分子机制，为确立将myoD起始表达时间差异的遗传机制作为提高生猪产肉量新靶标提供科学依据。

MyoD is a crucial switch in regulating muscle-specific gene transcription, which has been proven to induce multiple cell types into myoblast and facilitate myoblast fusing into myotube. However, previous studies focused mainly on the expression (expression level) of myoD in regulating myoblast differentiation and myotube formation. In our latest study concerning three pig breeds differing in meat production, Wuzhishan pig with the least meat production showed myoD mRNA expression at 21 days post coitus (dpc), Lantang pig with moderate meat production showed modicum myoD mRNA expression while Landrace with the highest meat production showed almost no expression of myoD mRNA. Thus, we reasonably deduce that distinct expression time of myoD in different pig breed embryos probably determine the differentiation time of myoblast and the numbers of myofibers, which in turn, leading to the distinction in meat production after birth. Moreover, in line with our expectations, at 21 dpc, Wuzhishan pig showed higher level of transcription promoting histone modification H3K4me3 than transcription repressing histone modification H3K27me3, which could facilitate myoblast differentiation status. Meanwhile, Landrace showed balanced modification of H3K4me3 and H3K27me3, which could promote myoblast proliferation status. This research aim to control myoD expression time in vitro and myoD inducible mice model with or without myf5 expression in accompany with Chip and other validating methods to illuminate the mechanism of distinct myoD expression time in pig breeds differing in meat production. This study will not only help better understand the mechanism involved in pig breeds differing in meat production, but also provide scientific evidence to increase meat production using genetic mechanism of distinct myoD expression time in the future.