VELCROs：长程染色质互作组合驱动染色质区室化
Varied Ensembles of Long-range ChROmatin interactions drive chromatin compartmentalization
研究在秀丽隐杆线虫（Caenorhabditis elegans）中分析了缺失不同染色质调控蛋白的存活突变体，发现 HP1 型因子 HPL-2 与 MBT 结构域蛋白 LIN-61 共同参与染色质区室化。两者与组蛋白修饰 H3K9me2 共同结合的基因组区域形成 30–50 kb 的宽界面，并发生组合式互作，作者将其命名为 VELCROs（Varied Ensembles of Long-range ChROmatin interactions）。
来源：Nucleic Acids Research · doi.org
The chromatin components that are involved in organizing eukaryotic genomes into active and inactive compartments remain unclear. In analysing viable Caenorhabditis elegans mutants lacking different chromatin-regulatory proteins, we found that the HP1-type factor HPL-2 and the MBT-domain protein LIN-61 jointly contribute to chromatin compartmentalization. Genomic regions bound by both proteins and their cognate histone mark H3 lysine 9 dimethylation (H3K9me2) form broad interfaces of 30–50 kilobases that engage in combinatorial interactions, which we term ‘Varied Ensembles of Long-range ChROmatin interactions’ (VELCROs). Remarkably, VELCROs are defined by high density of H3K9me2, HPL-2, and LIN-61 sites, but not by the intensity of their individual peaks. Mutants that display defective chromatin compartmentalization are impaired in VELCROs. Polymer simulations show that VELCROs can drive a phase transition that segregates B from A chromatin compartments depending on peak densities. Our work identifies VELCROs as stochastic ensembles of interactions constrained within defined chromatin hubs that shape genome compartmentalization.