Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel 4056, Switzerland.
Biozentrum, University of Basel, Klingelbergstrasse 50/70, Basel 4056, Switzerland.
Cell Rep. 2018 Sep 25;24(13):3503-3512. doi: 10.1016/j.celrep.2018.08.074.
Genes in higher eukaryotes are regulated by long-range interactions, which can determine what combination of genes is expressed in a chromosomal segment. The choice of the genes can display exclusivity, independence, or co-occurrence. We introduced a simple measure to quantify this interdependence in gene expression and differentiated mouse embryonic stem cells to neurons to measure the single-cell expression of the gene isoforms in the protocadherin (Pcdh) cluster, a key component of neuronal diversity. As the neuronal progenitors mature into neurons, expression of the gene isoforms in the Pcdh array is initially concurrent. Even though the number of the expressed genes is increasing during differentiation, the expression shifts toward exclusivity. The expression frequency correlates highly with CTCF binding to the promoters and follows dynamically the changes in the binding during the differentiation. These findings aid in understanding the interplay between cellular differentiation and stochastic gene choice.
高等真核生物中的基因受到长程相互作用的调控,这种作用可以决定在染色体片段中表达哪些基因组合。基因的选择可以表现出排他性、独立性或共同出现。我们引入了一种简单的方法来量化基因表达的这种相互依赖性,并将小鼠胚胎干细胞分化为神经元,以测量原钙黏蛋白(Pcdh)簇中基因亚型的单细胞表达,该基因簇是神经元多样性的关键组成部分。随着神经元前体成熟为神经元,Pcdh 基因簇中基因亚型的表达最初是同时进行的。尽管在分化过程中表达的基因数量增加,但表达逐渐变得具有排他性。表达频率与 CTCF 结合到启动子上高度相关,并随着分化过程中结合的变化而动态变化。这些发现有助于理解细胞分化和随机基因选择之间的相互作用。