Molecular Characterization of a Human Matrix Attachment Region Epigenetic Regulator

Matrix attachment regions (MAR) generally act as epigenetic regulatory sequences that increase gene expression, and they were proposed to partition chromosomes into loop-forming domains. However, their molecular mode of action remains poorly understood. Here, we assessed the possible contribution of the AT-rich core and adjacent transcription factor binding motifs to the transcription augmenting and anti-silencing effects of human MAR 1–68. Either flanking sequences together with the AT-rich core were required to obtain the full MAR effects. Shortened MAR derivatives retaining full MAR activity were constructed from combinations of the AT-rich sequence and multimerized transcription factor binding motifs, implying that both transcription factors and the AT-rich microsatellite sequence are required to mediate the MAR effect. Genomic analysis indicated that MAR AT-rich cores may be depleted of histones and enriched in RNA polymerase II, providing a molecular interpretation of their chromatin domain insulator and transcriptional augmentation activities.

基质附着区（Matrix Attachment Regions, MAR）通常作为表观遗传调控序列，可增强基因表达，且被认为可将染色体划分为形成环结构的结构域。然而，其分子作用模式仍未被充分阐明。本研究针对人类MAR 1–68的转录增强与抗沉默效应，评估了其AT富集核心区及相邻转录因子结合基序的潜在贡献。实验结果表明，完整的MAR效应需要侧翼序列与AT富集核心区共同发挥作用。研究人员通过将AT富集序列与多聚化转录因子结合基序组合，构建了保留完整MAR活性的截短型MAR衍生物，这表明转录因子与AT富集微卫星序列二者均为介导MAR效应所必需。基因组分析结果显示，MAR的AT富集核心区可能存在组蛋白缺失与RNA聚合酶II（RNA polymerase II）富集现象，这为其染色质结构域绝缘子活性与转录增强活性提供了分子层面的解释。