Genome Biology Program and ACRF Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, Garran Road, Acton, ACT 0200, Australia.
Genome Biol. 2009;10(10):R107. doi: 10.1186/gb-2009-10-10-r107. Epub 2009 Oct 6.
Specific chromatin characteristics, especially the modification status of the core histone proteins, are associated with active and inactive genes. There is growing evidence that genes that respond to environmental or developmental signals may possess distinct chromatin marks. Using a T cell model and both genome-wide and gene-focused approaches, we examined the chromatin characteristics of genes that respond to T cell activation.
To facilitate comparison of genes with similar basal expression levels, we used expression-profiling data to bin genes according to their basal expression levels. We found that inducible genes in the lower basal expression bins, especially rapidly induced primary response genes, were more likely than their non-responsive counterparts to display the histone modifications of active genes, have RNA polymerase II (Pol II) at their promoters and show evidence of ongoing basal elongation. There was little or no evidence for the presence of active chromatin marks in the absence of promoter Pol II on these inducible genes. In addition, we identified a subgroup of genes with active promoter chromatin marks and promoter Pol II but no evidence of elongation. Following T cell activation, we find little evidence for a major shift in the active chromatin signature around inducible gene promoters but many genes recruit more Pol II and show increased evidence of elongation.
These results suggest that the majority of inducible genes are primed for activation by having an active chromatin signature and promoter Pol II with or without ongoing elongation.
特定的染色质特征,特别是核心组蛋白的修饰状态,与活跃和非活跃的基因有关。越来越多的证据表明,对环境或发育信号做出反应的基因可能具有独特的染色质标记。我们使用 T 细胞模型和全基因组及基因聚焦方法,研究了对 T 细胞激活有反应的基因的染色质特征。
为了便于比较具有相似基础表达水平的基因,我们使用表达谱数据根据基础表达水平对基因进行分类。我们发现,在较低基础表达箱中的诱导基因,特别是快速诱导的初级反应基因,比它们的非反应基因更有可能显示出活跃基因的组蛋白修饰,在其启动子上具有 RNA 聚合酶 II(Pol II),并显示出正在进行的基础延伸的证据。在这些诱导基因中,如果没有启动子 Pol II,几乎没有或没有活跃染色质标记的存在。此外,我们鉴定了一组具有活跃启动子染色质标记和启动子 Pol II 但没有延伸证据的基因。在 T 细胞激活后,我们发现诱导基因启动子周围的活跃染色质特征几乎没有明显的变化,但许多基因招募了更多的 Pol II,并显示出延伸增加的证据。
这些结果表明,大多数诱导基因通过具有活跃的染色质特征和启动子 Pol II 来为激活做好准备,无论是否有正在进行的延伸。