Steglich Babett, Strålfors Annelie, Khorosjutina Olga, Persson Jenna, Smialowska Agata, Javerzat Jean-Paul, Ekwall Karl
Department of Biosciences and Nutrition; Center for Innovative Medicine, Karolinska Institutet, Novum Building, Huddinge, Sweden.
Univ. Bordeaux, Institut de Biochimie et Génétique Cellulaires, UMR 5095, Bordeaux, France; CNRS, Institut de Biochimie et Génétique Cellulaires, UMR 5095, Bordeaux, France.
PLoS Genet. 2015 Mar 23;11(3):e1005101. doi: 10.1371/journal.pgen.1005101. eCollection 2015 Mar.
In eukaryotic cells, local chromatin structure and chromatin organization in the nucleus both influence transcriptional regulation. At the local level, the Fun30 chromatin remodeler Fft3 is essential for maintaining proper chromatin structure at centromeres and subtelomeres in fission yeast. Using genome-wide mapping and live cell imaging, we show that this role is linked to controlling nuclear organization of its targets. In fft3∆ cells, subtelomeres lose their association with the LEM domain protein Man1 at the nuclear periphery and move to the interior of the nucleus. Furthermore, genes in these domains are upregulated and active chromatin marks increase. Fft3 is also enriched at retrotransposon-derived long terminal repeat (LTR) elements and at tRNA genes. In cells lacking Fft3, these sites lose their peripheral positioning and show reduced nucleosome occupancy. We propose that Fft3 has a global role in mediating association between specific chromatin domains and the nuclear envelope.
在真核细胞中,局部染色质结构和细胞核内的染色质组织都影响转录调控。在局部水平上,Fun30染色质重塑因子Fft3对于维持裂殖酵母着丝粒和亚端粒处的适当染色质结构至关重要。通过全基因组定位和活细胞成像,我们表明这一作用与控制其靶标的核组织有关。在fft3∆细胞中,亚端粒失去了与核周LEM结构域蛋白Man1的关联,并移动到细胞核内部。此外,这些区域中的基因上调,活性染色质标记增加。Fft3在逆转座子衍生的长末端重复(LTR)元件和tRNA基因处也富集。在缺乏Fft3的细胞中,这些位点失去其外周定位,并显示核小体占有率降低。我们提出Fft3在介导特定染色质结构域与核膜之间的关联中具有全局作用。