PDF(Pubmed)
Abstract：
Histone H1 participates in chromatin condensation and regulates nuclear processes. Human somatic cells may contain up to seven histone H1 variants, although their functional heterogeneity is not fully understood. Here, we have profiled the differential nuclear distribution of the somatic H1 repertoire in human cells through imaging techniques including super-resolution microscopy. H1 variants exhibit characteristic distribution patterns in both interphase and mitosis. H1.2, H1.3, and H1.5 are universally enriched at the nuclear periphery in all cell lines analyzed and co-localize with compacted DNA. H1.0 shows a less pronounced peripheral localization, with apparent variability among different cell lines. On the other hand, H1.4 and H1X are distributed throughout the nucleus, being H1X universally enriched in high-GC regions and abundant in the nucleoli. Interestingly, H1.4 and H1.0 show a more peripheral distribution in cell lines lacking H1.3 and H1.5. The differential distribution patterns of H1 suggest specific functionalities in organizing lamina-associated domains or nucleolar activity, which is further supported by a distinct response of H1X or phosphorylated H1.4 to the inhibition of ribosomal DNA transcription. Moreover, H1 variants depletion affects chromatin structure in a variant-specific manner. Concretely, H1.2 knock-down, either alone or combined, triggers a global chromatin decompaction. Overall, imaging has allowed us to distinguish H1 variants distribution beyond the segregation in two groups denoted by previous ChIP-Seq determinations. Our results support H1 variants heterogeneity and suggest that variant-specific functionality can be shared between different cell types.
摘要：
组蛋白H1参与染色质凝聚并调节核过程。人类体细胞可能包含多达七个组蛋白H1变体，尽管它们的功能异质性尚未完全了解。这里,我们通过包括超分辨率显微镜在内的成像技术分析了人体细胞H1库的差异核分布。H1变体在间期和有丝分裂中均表现出特征性的分布模式。在所有分析的细胞系中,H1.2、H1.3和H1.5普遍富集在核外围,并与压缩的DNA共定位。H1.0显示不太明显的外围定位，不同细胞系之间具有明显的变异性。另一方面,H1.4和HLX分布在整个细胞核中，在高GC区域普遍富集，在核仁中丰富。有趣的是,H1.4和H1.0在缺乏H1.3和H1.5的细胞系中显示出更外周的分布。H1的差异分布模式表明在组织层相关结构域或核仁活性中具有特定的功能，其进一步由对核糖体DNA转录的抑制的H1X或磷酸化H1.4的独特反应支持。此外，H1变体耗竭以变体特异性方式影响染色质结构。具体而言,H1.2击倒，无论是单独还是组合，触发全局染色质分解。总的来说,影像学检查使我们能够在先前ChIP-Seq测定所表示的两组中区分分离以外的H1变体分布.我们的结果支持H1变体异质性，并表明变体特异性功能可以在不同细胞类型之间共享。
