Mitosis is a cellular process that produces two identical progenies. Genome-wide transcription is believed to be silenced during mitosis. However, some transcription factors have been reported to associate with the mitotic chromatin to uphold a role in ‘gene-bookmarking’. Here, we investigated the dynamic role of nuclear receptor SHP during cell cycle, and observed intermolecular interactions with PXR and ERα. This was reflected in altered subcellular localization, transcription function and mitotic chromatin behavior of these receptors. Subsequently, by in silico and live cell imaging approaches we identified the minimal domain(s) and crucial amino-acid residues required for such receptor-receptor interactions. It was apparent that both PXR/ERα interact with SHP to translocate cytoplasmic RFP-tagged SHP into the nucleus. In addition, during mitosis SHP interacted with some of the key nuclear receptors, altering partners, as well as, its own relationship with mitotic chromatin. SHP displaced a major fraction of PXR and ERα from the mitotic chromatin while promoted its own weak association reflected in its binding. Since SHP lacks DBD this association is attributed to receptor-receptor interactions rather than SHP-DNA interactions. The abrogation of PXR and ERα from the mitotic chromatin by SHP implies potential implications in regulation of gene bookmarking events in cellular development. Overall, it is concluded that intermolecular interactions between SHP and partner PXR/ERα result in attenuation of target promoter activities. It is proposed that SHP may act as an indirect physiological regulator and functions in a hog-tie manner by displacing the interacting transcription factor from gene regulatory sites.

有丝分裂是产生两个相同后代的细胞过程。全基因组转录被认为在有丝分裂期间被沉默。然而，据报道，一些转录因子与有丝分裂染色质相关，以支持“基因书签”中的作用。在这里，我们研究了核受体 SHP 在细胞周期中的动态作用，并观察了与 PXR 和 ERα 的分子间相互作用。这反映在这些受体的亚细胞定位、转录功能和有丝分裂染色质行为的改变上。随后，通过in silico和活细胞成像方法，我们确定了这种受体 - 受体相互作用所需的最小结构域和关键氨基酸残基。很明显，PXR/ERα 与 SHP 相互作用，将细胞质 RFP 标记的 SHP 转移到细胞核中。此外，在有丝分裂期间，SHP 与一些关键的核受体相互作用，改变伙伴，以及它自己与有丝分裂染色质的关系。SHP 从有丝分裂染色质中取代了大部分 PXR 和 ERα，同时促进了其自身弱结合，反映在其结合中。由于 SHP 缺乏 DBD，因此这种关联归因于受体-受体相互作用，而不是 SHP-DNA 相互作用。SHP 从有丝分裂染色质中消除 PXR 和 ERα 暗示在细胞发育中基因书签事件的调节中具有潜在意义。全面的，得出的结论是，SHP 和伴侣 PXR/ERα 之间的分子间相互作用导致靶启动子活性减弱。有人提出，SHP 可能作为一种间接的生理调节剂，并在通过从基因调控位点置换相互作用的转录因子来实现hog-tie方式。