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染色质凝聚在粒细胞生成过程中对基因簇表达的调控作用。

The role of chromatin condensation during granulopoiesis in the regulation of gene cluster expression.

机构信息

Centre for Biomedical Image Analysis, Faculty of Informatics, Masaryk University, Czech Republic.

出版信息

Epigenetics. 2010 Nov-Dec;5(8):758-66. doi: 10.4161/epi.5.8.13183. Epub 2010 Nov 1.

Abstract

Changes in nuclear architecture play an important role in the regulation of gene expression. The importance of epigenetic changes is observed during granulopoiesis, when changes in the nuclear architecture are considered a major factor that influences the downregulation of genes. We aimed to assess the influence of chromatin condensation on the regulation of gene expression during granulopoiesis. Based on a previously published microarray analysis, we chose loci with different levels of transcriptional activity during granulopoiesis. Fluorescent in situ hybridisation (FISH) and immunofluorescent labelling of RNA polymerase II were used to determine the relationship between the transcriptional activity of gene clusters and their localisation within areas with different levels of chromatin condensation. Although active loci were positioned outside of areas of condensed chromatin, downregulation of genes during granulopoiesis was not accompanied by a shift of the downregulated loci to condensed areas. Only the beta-globin cluster was subjected to chromatin condensation and localised to condensed areas. Our results indicate that granulopoiesis is accompanied by a non-random, tissue-specific pattern of chromatin condensation. Furthermore, we observed that the decrease in the quantity of RNA polymerase II correlates with the differentiation process and likely acts in synergy with chromatin condensation to downregulate total gene expression.

摘要

核架构的改变在基因表达的调控中起着重要作用。在粒细胞发生过程中观察到表观遗传变化的重要性,此时核架构的改变被认为是影响基因下调的主要因素。我们旨在评估染色质凝聚对粒细胞发生过程中基因表达调控的影响。基于先前发表的微阵列分析,我们选择了粒细胞发生过程中转录活性不同的基因座。荧光原位杂交(FISH)和 RNA 聚合酶 II 的免疫荧光标记用于确定基因簇的转录活性与其在不同染色质凝聚水平区域内定位之间的关系。尽管活性基因座位于凝聚染色质区域之外,但粒细胞发生过程中基因的下调并不伴随着下调基因座向凝聚区域的转移。只有β-珠蛋白基因簇受到染色质凝聚的影响,并定位于凝聚区域。我们的结果表明,粒细胞发生伴随着非随机的、组织特异性的染色质凝聚模式。此外,我们观察到 RNA 聚合酶 II 的数量减少与分化过程相关,并且可能与染色质凝聚协同作用以下调总基因表达。

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