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有丝分裂染色体在通用的环状阵列构象中具有细胞类型和物种特异性的结构特征。

Mitotic chromosomes harbor cell type- and species-specific structural features within a universal loop array conformation.

作者信息

Oomen Marlies E, Fox A Nicole, Gonzalez Inma, Molliex Amandine, Papadopoulou Thaleia, Navarro Pablo, Dekker Job

机构信息

Department of Systems Biology, University of Massachusetts Chan Medical School, Worcester, Massachusetts 01605, USA.

Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA.

出版信息

Genome Res. 2025 Jul 8. doi: 10.1101/gr.280648.125.

Abstract

Mitotic chromosomes are considered to be universally folded as loop arrays across species and cell types. However, some studies suggest that features of mitotic chromosomes might be cell type- or species-specific. We previously reported that CTCF binding in human differentiated cell lines is lost in mitosis, whereas mitotic mouse embryonic stem cells (mESC) display prominent binding at a subset of CTCF sites. Here, we perform footprint ATAC-seq analyses of mESCs, and somatic mouse and human cells, confirming these findings. We then investigate roles of mitotically bookmarked CTCF in prometaphase chromosome organization by Hi-C. We do not find any remaining interphase structures, such as TADs or loops, at bookmarked CTCF sites in mESCs. This suggests that mitotic loop extruders condensin I and II are not blocked by CTCF and, thus, that maintained CTCF binding does not alter mitotic chromosome folding. Lastly, we compare mitotic Hi-C data generated in this study in mouse with public data in human and chicken. We do not find any cell type-specific differences; however, we find a difference between species. The average genomic size of mitotic loops is smaller in chicken (200-300 kb) compared to human (400-600 kb) and especially mouse (1-1.5 Mb). Interestingly, we find that this difference is correlated with the genomic length of q-arms in these species, a finding we confirm by microscopy measurements of chromosome compaction. This suggests that the dimensions of mitotic chromosomes can be modulated through control of loop size by condensins to facilitate species-appropriate shortening of chromosome arms.

摘要

有丝分裂染色体被认为在物种和细胞类型中普遍以环状阵列的形式折叠。然而,一些研究表明,有丝分裂染色体的特征可能是细胞类型或物种特异性的。我们之前报道过,在人类分化细胞系中,CTCF结合在有丝分裂过程中会丢失,而有丝分裂的小鼠胚胎干细胞(mESC)在一部分CTCF位点显示出显著的结合。在这里,我们对mESC、体细胞小鼠和人类细胞进行了足迹ATAC-seq分析,证实了这些发现。然后,我们通过Hi-C研究了有丝分裂时标记的CTCF在前中期染色体组织中的作用。我们在mESC中有丝分裂标记的CTCF位点没有发现任何剩余的间期结构,如TAD或环。这表明有丝分裂环状挤压蛋白凝缩素I和II不会被CTCF阻断,因此,持续的CTCF结合不会改变有丝分裂染色体的折叠。最后,我们将本研究中在小鼠中生成的有丝分裂Hi-C数据与人类和鸡的公开数据进行了比较。我们没有发现任何细胞类型特异性差异;然而,我们发现了物种之间的差异。与人类(400-600 kb)尤其是小鼠(1-1.5 Mb)相比,鸡的有丝分裂环的平均基因组大小较小(200-300 kb)。有趣的是,我们发现这种差异与这些物种中q臂的基因组长度相关,我们通过染色体压缩的显微镜测量证实了这一发现。这表明有丝分裂染色体的尺寸可以通过凝缩素对环大小的控制来调节,以促进适合物种的染色体臂缩短。

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