From the Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad-500007, India.
From the Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad-500007, India
Mol Cell Proteomics. 2018 Oct;17(10):1965-1978. doi: 10.1074/mcp.RA118.000591. Epub 2018 Jul 10.
Chromatin condenses several folds to form mitotic chromosomes during cell division and decondenses post-mitotically to reoccupy their nuclear territory and regain their specific transcriptional profile in a precisely lineage specific manner. This necessitates that the features of nuclear architecture and DNA topology persist through mitosis. We compared the proteome of nuclease and high salt resistant fraction of interphase nucleus known as nuclear matrix (NuMat) and an equivalent biochemical fraction in the mitotic chromosome known as mitotic chromosome scaffold (MiCS). Our study elucidates that as much as 67% of the NuMat proteins are retained in the MiCS indicating that the features of nuclear architecture in interphase nucleus are retained on the mitotic chromosomes. Proteins of the NuMat/MiCS have large dynamic range of MS signal and were detected in sub-femtomolar amounts. Chromatin/RNA binding proteins with hydrolase and helicase activity are highly enriched in NuMat as well as MiCS. Although several transcription factors involved in functioning of interphase nucleus are present exclusively in NuMat, protein components responsible for assembly of membrane-less nuclear bodies are uniquely retained in MiCS. Our study clearly indicates that the features of nuclear architecture, in the structural context of NuMat, are retained in MiCS and possibly play an important role in maintenance of cell lineage specific transcriptional status during cell division and thereby, serve as components of cellular memory.
染色质在细胞分裂过程中折叠数倍形成有丝分裂染色体,有丝分裂后解压缩,重新占据其核区,并以精确的谱系特异性方式恢复其特定的转录谱。这就需要核结构和 DNA 拓扑结构的特征在有丝分裂过程中保持不变。我们比较了间期核的核酶和高盐抗性部分(称为核基质(NuMat))和有丝分裂染色体中称为有丝分裂染色体支架(MiCS)的等效生化部分的蛋白质组。我们的研究表明,多达 67%的 NuMat 蛋白保留在 MiCS 中,这表明间期核的核结构特征在有丝分裂染色体上得以保留。NuMat/MiCS 的蛋白质具有很大的 MS 信号动态范围,在亚飞摩尔水平检测到。具有水解酶和螺旋酶活性的染色质/RNA 结合蛋白在 NuMat 和 MiCS 中高度富集。虽然参与间期核功能的几个转录因子仅存在于 NuMat 中,但负责组装无膜核体的蛋白质成分仅保留在 MiCS 中。我们的研究清楚地表明,NuMat 中核结构的特征在 MiCS 中得以保留,并可能在细胞分裂过程中维持细胞谱系特异性转录状态方面发挥重要作用,从而成为细胞记忆的组成部分。