Department of Cell and Developmental Biology, John Innes Centre, Norwich, UK.
EMBO J. 2013 Jan 9;32(1):140-8. doi: 10.1038/emboj.2012.324. Epub 2012 Dec 7.
Gene activation in eukaryotes frequently involves interactions between chromosomal regions. We have investigated whether higher-order chromatin structures are involved in the regulation of the Arabidopsis floral repressor gene FLC, a target of several chromatin regulatory pathways. Here, we identify a gene loop involving the physical interaction of the 5' and 3' flanking regions of the FLC locus using chromosome conformation capture. The FLC loop is unaffected by mutations disrupting conserved chromatin regulatory pathways leading to very different expression states. However, the loop is disrupted during vernalization, the cold-induced, Polycomb-dependent epigenetic silencing of FLC. Loop disruption parallels timing of the cold-induced FLC transcriptional shut-down and upregulation of FLC antisense transcripts, but does not need a cold-induced PHD protein required for the epigenetic silencing. We suggest that gene loop disruption is an early step in the switch from an expressed to a Polycomb-silenced state.
真核生物中的基因激活通常涉及染色体区域之间的相互作用。我们研究了是否更高阶的染色质结构参与调控拟南芥花抑制基因 FLC,该基因是几个染色质调控途径的靶标。在这里,我们使用染色体构象捕获鉴定了一个基因环,涉及 FLC 基因座的 5'和 3'侧翼区域的物理相互作用。该 FLC 环不受破坏导致非常不同表达状态的保守染色质调控途径的突变的影响。然而,在春化过程中,FLC 被冷诱导、多梳依赖性的表观遗传沉默,该环会被打断。环的破坏与冷诱导的 FLC 转录关闭以及 FLC 反义转录本的上调时间一致,但不需要冷诱导的 PHD 蛋白,该蛋白是表观遗传沉默所必需的。我们认为基因环的破坏是从表达状态到多梳沉默状态的转变的早期步骤。