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Nac1 促进多能性基因激活,建立体细胞重编程。

Nac1 facilitates pluripotency gene activation for establishing somatic cell reprogramming.

机构信息

Laboratory of Stem Cells & Cell reprogramming, Department of Biomedical Engineering, Dongguk University, Seoul, 100-715, Republic of Korea.

Database Laboratory, Department of Computer Science and Engineering, Dongguk University, Pildong-ro 1-gil 30, Jung-gu, Seoul, 04620, Republic of Korea.

出版信息

Biochem Biophys Res Commun. 2019 Oct 15;518(2):253-258. doi: 10.1016/j.bbrc.2019.08.043. Epub 2019 Aug 12.

Abstract

Transcription factors play a central role in pluripotency transcription circuitry for establishing pluripotent reprogramming. Master transcription factors Oct4, Nanog, and Sox2 are known to form the core of the pluripotency transcription network. Other transcription factors also play critical roles for further refining the core circuitry for pluripotency in induced pluripotent stem (iPS) cells. Here, we reported that Nac1 interacted with the master pluripotent factors Oct4 and Nanog co-occupies gene promoters bound by these transcriptional factors for establishing pluripotency. Moreover, this interaction coordinates gene expression with H3K4me3 in the somatic cell reprogramming. Knockdown of Nac1 suppressed somatic cell reprogramming, whereas overexpression of Nac1 resulted in enhanced efficiency of induced pluripotent cell generation. Altogether, these results reveal the genome wide role for Nac1 in the contribution to the pluripotency circuitry and the regulation of the establishing pluripotent state.

摘要

转录因子在多能性转录回路中发挥核心作用,用于建立多能性重编程。众所周知,主转录因子 Oct4、Nanog 和 Sox2 形成多能性转录网络的核心。其他转录因子也在进一步细化诱导多能干细胞 (iPS) 细胞中的多能性核心回路方面发挥着关键作用。在这里,我们报道了 Nac1 与主多能因子 Oct4 和 Nanog 相互作用,共同占据这些转录因子结合的基因启动子,从而建立多能性。此外,这种相互作用协调了体细胞重编程过程中的基因表达与 H3K4me3。Nac1 的敲低抑制了体细胞重编程,而过表达 Nac1 则导致诱导多能细胞生成效率的提高。总之,这些结果揭示了 Nac1 在多能性回路中的全基因组作用以及对建立多能状态的调控作用。

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