4月12日，國際著名雜志Science在線刊登了國外研究人員的最新研究成果“Epigenomic Enhancer Profiling Defines a Signature of Colon Cancer,，”，文章中,，研究者發(fā)現(xiàn)了一種能精確指示結(jié)腸直腸細(xì)胞是癌性的表觀遺傳學(xué)特征。
在一個人的DNA中除了編碼的遺傳指令之外,，許多表觀遺傳因子，或?qū)蚪M所做的非編碼性但也是功能性的修該,，會顯著地影響在健康及生病的人中的基因表達(dá),。如今，研究人員發(fā)現(xiàn)了一種似乎能精確地指示結(jié)腸直腸細(xì)胞是癌性的表觀遺傳學(xué)特征—一種特定的獲得及失去染色質(zhì)標(biāo)記的模式,。
Batool Akhtar-Zaidi及其同事們用一種叫做組蛋白H3賴氨酸4,，或H3K4的甲基化形式的蛋白質(zhì)——它標(biāo)記了多種所謂的基因增強(qiáng)子——來搜尋在癌性結(jié)腸細(xì)胞和正常結(jié)腸隱窩細(xì)胞中的這樣的表觀遺傳因子，而結(jié)腸癌最終是從結(jié)腸隱窩細(xì)胞中衍生出來的,。這些研究人員能夠在結(jié)腸直腸癌細(xì)胞中發(fā)現(xiàn)數(shù)千個或失或得的甲基化的H3K4位點(diǎn),。他們說，與這些增強(qiáng)子位點(diǎn)相關(guān)連的基因似乎富集了在結(jié)腸直腸癌中通常被中斷的通路,，并富含被認(rèn)為是警示標(biāo)志的基因變異,。綜合來看，這些研究人員的發(fā)現(xiàn)提示,，對基因組上的這些特定位點(diǎn)的表觀遺傳學(xué)改變驅(qū)動著一個促發(fā)結(jié)腸直腸癌的獨(dú)特的轉(zhuǎn)錄程序,。（生物谷Bioon.com）
doi:10.1126/science.1217277
PMC:
PMID:
Epigenomic Enhancer Profiling Defines a Signature of Colon Cancer
Batool Akhtar-Zaidi1, Richard Cowper-Sal·lari2, Olivia Corradin1, Alina Saiakhova1, Cynthia F. Bartels1, Dheepa Balasubramanian1, Lois Myeroff3, James Lutterbaugh3, Awad Jarrar4, Matthew F. Kalady3,4,5, Joseph Willis3,6, Jason H. Moore2, Paul J. Tesar1,3, Thomas Laframboise1,3, Sanford Markowitz1,3,7, Mathieu Lupien2,8, Peter C. Scacheri1,3,*
Cancer is characterized by gene expression aberrations. Studies have largely focused on coding sequences and promoters, despite the fact that distal regulatory elements play a central role in controlling transcription patterns. Here, we utilize the histone mark H3K4me1 to analyze gain and loss of enhancer activity genome wide in primary colon cancer lines relative to normal colon crypts. We identified thousands of variant enhancer loci (VELs) that comprise a signature that is robustly predictive of the in vivo colon cancer transcriptome. Furthermore, VELs are enriched in haplotype blocks containing colon cancer genetic risk variants, implicating these genomic regions in colon cancer pathogenesis. We propose that reproducible changes in the epigenome at enhancer elements drive a unique transcriptional program to promote colon carcinogenesis.
