Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms.
Single mammalian cells compensate for differences in cellular volume and DNA copy number through independent global transcriptional mechanisms.
复制标题
DOI：
10.1016/j.molcel.2015.03.005
复制
发表时间：
2015-04-16
期刊：
影响因子：
16
通讯作者：
Raj, Arjun
中科院分区：
文献类型：
--
作者：
Padovan-Merhar, Olivia;Nair, Gautham P.;Biaesch, Andrew G.;Mayer, Andreas;Scarfone, Steven;Foley, Shawn W.;Wu, Angela R.;Churchman, L. Stirling;Singh, Abhyudai;Raj, Arjun
单个哺乳动物细胞在细胞体积上表现出很大的变异性，即使在绝对DNA含量相同的情况下也是如此，因此必须补偿DNA浓度的差异才能保持基因表达产物的恒定浓度。利用单分子计数和计算图像分析，我们发现由于较大细胞中整体转录的增加，转录本丰度与细胞体积在单细胞水平上相关。细胞融合实验证明，增加细胞含量本身可以直接增加转录。定量分析表明，这一机制测量了细胞体积与DNA含量的比率，很可能是通过将转录因子隔离到DNA上。对转录猝发的分析揭示了DNA复制后基因剂量补偿的单独机制，使S早期和晚期的适当转录输出成为可能。我们的结果为定量理解DNA含量、细胞大小和单个细胞中基因表达可变性之间的关系提供了一个框架。
Individual mammalian cells exhibit large variability in cellular volume even with the same absolute DNA content and so must compensate for differences in DNA concentration in order to maintain constant concentration of gene expression products. Using single molecule counting and computational image analysis, we show that transcript abundance correlates with cellular volume at the single cell level due to increased global transcription in larger cells. Cell fusion experiments establish that increased cellular content itself can directly increase transcription. Quantitative analysis shows that this mechanism measures the ratio of cellular volume to DNA content, mostly likely through sequestration of a transcriptional factor to DNA. Analysis of transcriptional bursts reveals a separate mechanism for gene dosage compensation after DNA replication that enables proper transcriptional output during early and late S-phase. Our results provide a framework for quantitatively understanding the relationships between DNA content, cell size and gene expression variability in single cells.
登录
查看更多内容
影响因子：
9.8
作者：
das Neves RP;Jones NS;Andreu L;Gupta R;Enver T;Iborra FJ
通讯作者：
Iborra FJ
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
活细胞中 RNA 聚合酶 II 的转录周期。
影响因子：
7.8
作者：
Kimura, Hiroshi;Sugaya, Kimihiko;Cook, Peter R
通讯作者：
Cook, Peter R
影响因子：
6.1
作者：
Bryan AK;Hecht VC;Shen W;Payer K;Grover WH;Manalis SR
通讯作者：
Manalis SR
DOI：
10.1073/pnas.1119407109
发表时间：
2012-05-15
影响因子：
11.1
作者：
Bowsher, Clive G.;Swain, Peter S.
通讯作者：
Swain, Peter S.