稱作染色質(zhì)修飾化學(xué)標(biāo)記(綠色)激活稱作遠(yuǎn)程控制器的增強(qiáng)子(黃色)，將一個(gè)基因(紅色)開啟或關(guān)閉,。圖片來自 EMBL/P. Riedinger,。
當(dāng)胚胎發(fā)育時(shí),，不同細(xì)胞中不同基因被打開以便形成肌肉,、神經(jīng)元和身體其他部分。在每個(gè)細(xì)胞的細(xì)胞核內(nèi)部,，稱作增強(qiáng)子的基因序列發(fā)揮著類似遠(yuǎn)程控制器(remote control)的作用,，打開和關(guān)閉基因。如今,，德國海德爾堡歐洲分子生物學(xué)實(shí)驗(yàn)室(European Molecular Biology Laboratory, EMBL)科學(xué)家能夠精確地觀察和預(yù)測(cè)何時(shí)激活真實(shí)胚胎中的每個(gè)遠(yuǎn)程控制器,。2012年1月9日，他們的研究成果發(fā)表在《自然-遺傳學(xué)》期刊上,。
來自EMBL的 Eileen Furlong實(shí)驗(yàn)室的Stefan Bonn,，Robert Zinzen和Charles Girardot發(fā)現(xiàn)在發(fā)育過程中在精確的時(shí)間內(nèi)，將染色質(zhì)修飾---促進(jìn)或阻礙基因表達(dá)的化學(xué)標(biāo)記---的特異性組合放置在增強(qiáng)子上或者從增強(qiáng)子上移除,，從而開啟或關(guān)閉這些遠(yuǎn)程控制器,。
Furlong說，“在發(fā)育中的多細(xì)胞胚胎里,，我們的新方法提供關(guān)于基因和增強(qiáng)子活性狀態(tài)的細(xì)胞類型特異性信息,。”
科學(xué)家研究了已知的增強(qiáng)子，在果蠅發(fā)育的特定時(shí)間稱作中胚層(mesoderm)的細(xì)胞類型里比較了激活的增強(qiáng)子和失活的增強(qiáng)子,。他們注意到這些增強(qiáng)子中每一個(gè)擁有哪些染色質(zhì)修飾,，并設(shè)計(jì)出一種計(jì)算機(jī)模型，這樣單就基于它攜帶的染色質(zhì)標(biāo)記,，就可準(zhǔn)確滴預(yù)測(cè)一個(gè)增強(qiáng)子是活性的或失活的,。
在未來，這些科學(xué)家計(jì)劃使用這種方法在胚胎發(fā)育的不斷階段不同的組織類型中,，研究增強(qiáng)子的活性狀態(tài)和稱作轉(zhuǎn)錄因子的關(guān)鍵開關(guān)的存在之間的相互作用,，以便獲得單個(gè)細(xì)胞如何長成一個(gè)復(fù)雜有機(jī)體的更加完整的全貌。(生物谷：towersimper編譯)
doi:10.1038/ng.1064
PMC:
PMID:
Tissue-specific analysis of chromatin state identifies temporal signatures of enhancer activity during embryonic development
Stefan Bonn, Robert P Zinzen, Charles Girardot, E Hilary Gustafson, Alexis Perez-Gonzalez, Nicolas Delhomme,Yad Ghavi-Helm, Bartek Wilczyński, Andrew Riddell & Eileen E M Furlong
Chromatin modifications are associated with many aspects of gene expression, yet their role in cellular transitions during development remains elusive. Here, we use a new approach to obtain cell type–specific information on chromatin state and RNA polymerase II (Pol II) occupancy within the multicellular Drosophila melanogaster embryo. We directly assessed the relationship between chromatin modifications and the spatio-temporal activity of enhancers. Rather than having a unique chromatin state, active developmental enhancers show heterogeneous histone modifications and Pol II occupancy. Despite this complexity, combined chromatin signatures and Pol II presence are sufficient to predict enhancer activity de novo. Pol II recruitment is highly predictive of the timing of enhancer activity and seems dependent on the timing and location of transcription factor binding. Chromatin modifications typically demarcate large regulatory regions encompassing multiple enhancers, whereas local changes in nucleosome positioning and Pol II occupancy delineate single active enhancers. This cell type–specific view identifies dynamic enhancer usage, an essential step in deciphering developmental networks.
