最新一期的Nature Genetics在線版刊登了三篇文章,，三個(gè)獨(dú)立的研究團(tuán)隊(duì)解決了系統(tǒng)生物學(xué)理論中最重要的理論,，三文章釋放了一系列的數(shù)據(jù)解答了系統(tǒng)生物學(xué)細(xì)胞定向分化的關(guān)鍵調(diào)控網(wǎng)絡(luò)。同期Nature配發(fā)了評論文章,，F(xiàn)ANTOM studies networks in cells,。
系統(tǒng)生物學(xué)研究的最終目的在于解決細(xì)胞定向分化的路徑，實(shí)現(xiàn)這一目標(biāo)不僅有助人類深入了解整體發(fā)育,，更有利于人們探索干細(xì)胞治療領(lǐng)域（要實(shí)現(xiàn)干細(xì)胞治療目的,，首先要掌握干細(xì)胞定向分化理論知識和技術(shù)）。
這三個(gè)獨(dú)立的研究實(shí)驗(yàn)室都屬于FANTOM項(xiàng)目的實(shí)驗(yàn)室,，F(xiàn)ANTOM項(xiàng)目旨在深入研究人類基因調(diào)控網(wǎng)絡(luò),。目前全球有100多個(gè)實(shí)驗(yàn)室參加了這一項(xiàng)目，該項(xiàng)目主要利用RNA測序技術(shù)將RNA序列數(shù)據(jù)與DNA序列數(shù)據(jù)相比較,，鑒定基因轉(zhuǎn)錄的起始位點(diǎn),。
本期Nature Genetics上的三篇文章的發(fā)布者都屬于FANTOM項(xiàng)目實(shí)驗(yàn)室，第一個(gè)研究小組鑒定出一系列的動(dòng)物基因轉(zhuǎn)錄起始位點(diǎn),，這一研究屬于FANTOM4項(xiàng)目,，目前已經(jīng)鑒定了人類，雞和果蠅的轉(zhuǎn)錄起始位點(diǎn)的小RNA,，大小在18nt左右,。
第二篇文章的研究項(xiàng)目也屬于FANTOM4計(jì)劃，通過全基因組掃描技術(shù)鑒定出23000個(gè)候選反轉(zhuǎn)錄轉(zhuǎn)座子調(diào)節(jié)序列,。功能研究顯示,，這些反轉(zhuǎn)錄轉(zhuǎn)座子的轉(zhuǎn)錄調(diào)節(jié)序列對哺乳動(dòng)物的轉(zhuǎn)錄結(jié)果具有重要的影響。
第三篇文章的屬于FANTOM4項(xiàng)目,，選用人類單核細(xì)胞為研究對象,，鑒定出人類骨髓性白血病細(xì)胞系的轉(zhuǎn)錄調(diào)控網(wǎng)絡(luò)。這些研究結(jié)果表明,，多種轉(zhuǎn)錄因子組成復(fù)雜的網(wǎng)絡(luò),，共同調(diào)節(jié)細(xì)胞的生長和分化，沒有單個(gè)的轉(zhuǎn)錄因子唯一的調(diào)控因子,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Genetics 19 April 2009 | doi:10.1038/ng.312
Tiny RNAs associated with transcription start sites in animals
Ryan J Taft1, Evgeny A Glazov2, Nicole Cloonan1, Cas Simons1, Stuart Stephen1, Geoffrey J Faulkner1, Timo Lassmann3, Alistair R R Forrest3,4, Sean M Grimmond1, Kate Schroder1, Katharine Irvine1, Takahiro Arakawa3, Mari Nakamura3, Atsutaka Kubosaki3, Kengo Hayashida3, Chika Kawazu3, Mitsuyoshi Murata3, Hiromi Nishiyori3, Shiro Fukuda3, Jun Kawai3, Carsten O Daub3, David A Hume1,5, Harukazu Suzuki3, Valerio Orlando6,7, Piero Carninci3, Yoshihide Hayashizaki3 & John S Mattick1
It has been reported that relatively short RNAs of heterogeneous sizes are derived from sequences near the promoters of eukaryotic genes. In conjunction with the FANTOM4 project, we have identified tiny RNAs with a modal length of 18 nt that map within -60 to +120 nt of transcription start sites (TSSs) in human, chicken and Drosophila. These transcription initiation RNAs (tiRNAs) are derived from sequences on the same strand as the TSS and are preferentially associated with G+C-rich promoters. The 5' ends of tiRNAs show peak density 10–30 nt downstream of TSSs, indicating that they are processed. tiRNAs are generally, although not exclusively, associated with highly expressed transcripts and sites of RNA polymerase II binding. We suggest that tiRNAs may be a general feature of transcription in metazoa and possibly all eukaryotes.
Nature Genetics 19 April 2009 | doi:10.1038/ng.368
The regulated retrotransposon transcriptome of mammalian cells
Geoffrey J Faulkner1, Yasumasa Kimura2, Carsten O Daub2, Shivangi Wani1, Charles Plessy2, Katharine M Irvine3, Kate Schroder3, Nicole Cloonan1, Anita L Steptoe1, Timo Lassmann2, Kazunori Waki2, Nadine Hornig4,5, Takahiro Arakawa2, Hazuki Takahashi2, Jun Kawai2, Alistair R R Forrest2,6, Harukazu Suzuki2, Yoshihide Hayashizaki2, David A Hume7, Valerio Orlando4,5, Sean M Grimmond1 & Piero Carninci2
Although repetitive elements pervade mammalian genomes, their overall contribution to transcriptional activity is poorly defined. Here, as part of the FANTOM4 project, we report that 6–30% of cap-selected mouse and human RNA transcripts initiate within repetitive elements. Analysis of approximately 250,000 retrotransposon-derived transcription start sites shows that the associated transcripts are generally tissue specific, coincide with gene-dense regions and form pronounced clusters when aligned to full-length retrotransposon sequences. Retrotransposons located immediately 5' of protein-coding loci frequently function as alternative promoters and/or express noncoding RNAs. More than a quarter of RefSeqs possess a retrotransposon in their 3' UTR, with strong evidence for the reduced expression of these transcripts relative to retrotransposon-free transcripts. Finally, a genome-wide screen identifies 23,000 candidate regulatory regions derived from retrotransposons, in addition to more than 2,000 examples of bidirectional transcription. We conclude that retrotransposon transcription has a key influence upon the transcriptional output of the mammalian genome.
Nature Genetics 19 April 2009 | doi:10.1038/ng.375
The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line
The FANTOM Consortium, Riken Omics Science Center1 &
Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites, we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process.
