Orsztynowicz Maciej, Lechniak Dorota, Pawlak Piotr, Kociucka Beata, Kubickova Svatava, Cernohorska Halina, Madeja Zofia Eliza
Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland.
Veterinary Research Institute, Brno, Czech Republic.
PLoS One. 2017 Aug 2;12(8):e0182398. doi: 10.1371/journal.pone.0182398. eCollection 2017.
Loss of totipotentcy in an early embryo is directed by molecular processes responsible for cell fate decisions. Three dimensional genome organisation is an important factor linking chromatin architecture with stage specific gene expression patterns. Little is known about the role of chromosome organisation in gene expression regulation of lineage specific factors in mammalian embryos. Using bovine embryos as a model we have described these interactions at key developmental stages. Three bovine chromosomes (BTA) that differ in size, number of carried genes, and contain loci for key lineage regulators OCT4, NANOG and CDX2, were investigated. The results suggest that large chromosomes regardless of their gene density (BTA12 gene-poor, BTA5 gene-rich) do not significantly change their radial position within the nucleus. Gene loci however, may change its position within the chromosome territory (CT) and relocate its periphery, when stage specific process of gene activation is required. Trophectoderm specific CDX2 and epiblast precursor NANOG loci tend to locate on the surface or outside of the CTs, at stages related with their high expression. We postulate that the observed changes in CT shape reflect global alternations in gene expression related to differentiation.
早期胚胎中全能性的丧失由负责细胞命运决定的分子过程所引导。三维基因组组织是将染色质结构与阶段特异性基因表达模式联系起来的一个重要因素。关于染色体组织在哺乳动物胚胎中谱系特异性因子基因表达调控中的作用,我们知之甚少。以牛胚胎为模型,我们描述了关键发育阶段的这些相互作用。研究了三条大小、携带基因数量不同且包含关键谱系调节因子OCT4、NANOG和CDX2基因座的牛染色体(BTA)。结果表明,大染色体无论其基因密度如何(BTA12基因贫乏,BTA5基因丰富),在细胞核内的径向位置都不会显著改变。然而,当需要基因激活的阶段特异性过程时,基因座可能会改变其在染色体区域(CT)内的位置并重新定位到其周边。滋养外胚层特异性CDX2和上胚层前体NANOG基因座在与其高表达相关的阶段倾向于定位在CT的表面或外部。我们推测,观察到的CT形状变化反映了与分化相关的基因表达的整体变化。