胚胎干細胞的面前有兩條道路一一繼續(xù)自我更新或者分化成其它細胞類型,。這是一個兩難的選擇，需要許多復雜的基因調控途徑環(huán)路進行監(jiān)控,，這些關鍵的調控因子就是所謂的“首要轉錄因子”（master transcription factors）,，即控制基因表達開啟或關閉的蛋白。
在過去的幾年當中,，Whitehead生物醫(yī)學研究所(Whitehead Institute for Biomedical Research）Richard Young實驗室的研究人員繪制出了這個調控環(huán)路的關鍵部分,，但是這個圖譜中仍然缺少一些小RNA分子，即microRNAs,。microRNA小分子成為了研究熱點,，這種RNA生物體內源長度約為 20-23個核苷酸的非編碼小RNA，通過與靶mRNA的互補配對而在轉錄后水平上對基因的表達進行負調控,，導致mRNA的降解或翻譯抑制,。研究發(fā)現(xiàn)miRNA在大多數動物和植物的基因調控方面扮演著關鍵的角色。 （Bioon）
由于miRNAs是指導干細胞是否保持原有狀態(tài)的第二套調控因子,，因此在發(fā)育中扮演了重要的角色,。為了搞清楚miRNAs的作用,，Young和他的同事進行了進一步的研究，將干細胞圖譜上缺失的這一塊“拼圖”補上,，并將研究成果公布在了最新（8月8日）的Cell雜志上,。
在這項研究中，Young等人發(fā)現(xiàn)了miRNAs如何參與胚胎干細胞環(huán)路圖譜中的,，并且利用這張圖譜,，科學家們朝著了解成熟細胞如何重新編程，回到胚胎狀態(tài),，再分化成其它類型細胞的過程又邁進了一步,，也增進了對于癌癥及其它疾病中miRNA的作用的了解,。（生物谷Bioon.com）
物谷推薦原始出處：
Cell, Vol 134, 521-533, 08 August 2008
Connecting microRNA Genes to the Core Transcriptional Regulatory Circuitry of Embryonic Stem Cells
Alexander Marson,1,2,5 Stuart S. Levine,1,5 Megan F. Cole,1,2 Garrett M. Frampton,1,2 Tobias Brambrink,1 Sarah Johnstone,1,2 Matthew G. Guenther,1 Wendy K. Johnston,1,3 Marius Wernig,1 Jamie Newman,1,2 J. Mauro Calabrese,2,4 Lucas M. Dennis,1,2 Thomas L. Volkert,1 Sumeet Gupta,1 Jennifer Love,1 Nancy Hannett,1 Phillip A. Sharp,2,4 David P. Bartel,1,2,3 Rudolf Jaenisch,1,2 and Richard A. Young1,2,
1 Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
2 Department of Biology, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
3 Howard Hughes Medical Institute, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
4 Koch Institute, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA
Corresponding author
Richard A. Young
[email protected]
Summary
MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here the transcriptional regulatory circuitry of ES cells that incorporates protein-coding and miRNA genes based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb group proteins in ES cells and shows tissue-specific expression in differentiated cells. These data reveal how key ES cell transcription factors promote the ES cell miRNA expression program and integrate miRNAs into the regulatory circuitry controlling ES cell identity.
