Iwasaki Osamu, Tanizawa Hideki, Kim Kyoung-Dong, Yokoyama Yuhki, Corcoran Christopher J, Tanaka Atsunari, Skordalakes Emmanuel, Showe Louise C, Noma Ken-Ichi
The Wistar Institute, Philadelphia, PA19104, USA.
The Wistar Institute, Philadelphia, PA19104, USA.
Mol Cell. 2015 Sep 3;59(5):755-67. doi: 10.1016/j.molcel.2015.07.007. Epub 2015 Aug 6.
Genome/chromosome organization is highly ordered and controls various nuclear events, although the molecular mechanisms underlying the functional organization remain largely unknown. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosomal organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation.
基因组/染色体组织高度有序,并控制着各种核事件,尽管功能组织背后的分子机制在很大程度上仍然未知。在这里,我们表明,TATA框结合蛋白(TBP)与凝聚素的Cnd2 kleisin亚基相互作用,以介导裂殖酵母中的间期和有丝分裂染色体组织。TBP将凝聚素招募到RNA聚合酶III转录(Pol III)基因和高度转录的Pol II基因上;凝聚素反过来将这些基因与着丝粒联系起来。抑制Cnd2-TBP相互作用会破坏凝聚素在全基因组中的定位以及有丝分裂染色体的正确组装,导致染色体分离出现严重缺陷,并最终导致细胞死亡。我们提出,Cnd2-TBP相互作用通过将分散的基因座与着丝粒连接起来,协调转录与染色体结构。这种染色体排列有助于在动粒处将物理力有效地传递到染色体臂,从而支持染色体分离的保真度。