摘要
细胞核内部的空间排布并不是随机的,而是高度动态且具细胞特异性的。在发育过程中,序列特异性的转录调控因子和表观遗传修饰因子的协同作用及其核定位与基因的表达调控密切相关。我们前期研究发现,在成肌细胞中,同源异型框蛋白Msx1通过重新分布Ezh2复合物和抑制标记H3K27me3到细胞核核周来调控靶标基因的表达,从而抑制成肌细胞的分化。这种机制是成肌细胞所特有的,还是Msx1在抑制非成肌细胞分化时也会重新分布Ezh2复合物和转录抑制性标记H3K27me3到细胞核核周,目前还不清楚。在发育过程中,Msx1可以抑制乳腺上皮细胞HC11和成骨细胞BMP2T3的分化,因此我们选取了这两种非成肌细胞做进一步探究。我们发现,在这两种非肌肉细胞中,Msx1虽也富集在细胞核核周,却并不能重新分布Ezh2和转录抑制性标记H3K27me3到细胞核核周。我们的研究表明Msx1重新分布Ezh2和抑制性标记H3K27me3到细胞核核周具有细胞类型特异性。提示我们,Msx1可能是通过不同的分子机制来调控不同类型细胞的分化。
The spatial organization of materials in nucleus is not random, but highly dynamic and cell-specific. In the development process, the concerted action of sequence-specific transcriptional regulators and epigenetic modifiers, as well as their nuclear localization, are closely associated with the regulation of gene expression. Our previous study have indicated that, in myoblast cells, homeobox protein Msxl could regulate the expression of its target genes through redistributing Ezh2 complex and inhibiting the H3K27me3 repressive mark to the nuclear periphery, thus inhibiting the differentiation of myoblast cells. It has been unclear whether this mechanism is specific for myoblast cells or Msxl also could redistribute Ezh2 complex and the H3K27me3 repressive mark to the nuclear periphery in nonmyoblast cells. Msxl could inhibit the differentiation of breast epithelial cells HC11 and osteoblast cells BMP2T3 in development process, so we selected these two types of nonmyoblast cells for further study. We found that in these two kinds of nonmyoblast cells, though Msxl enriched at the nuclear periphery, it did not redistribute Ezh2 and the H3K27me3 repressive mark to the nuclear periphery. Our study illustrated that the redistribution of Ezh2 and the H3K27me3 repressive mark to the nuclear periphery by Msxl was cell-specific. These findings reminded us that the homeoprotein Msxl might regulate the differentiation ofdifferent kinds of cells through different molecular mechanisms.
出处
《基因组学与应用生物学》
CAS
CSCD
北大核心
2017年第6期2198-2204,共7页
Genomics and Applied Biology
基金
国家自然科学基金(31501053)
上海市浦江人才计划(14PJ1401300)共同资助