浅谈染色质高级结构与基因转录的远程调控

High-ordered Chromatin Structure and Long-range Regulation of Gene Transcription

精确的基因表达调控是细胞分化、个体发育和细胞维持正常生命活动的必要条件,转录调控是真核细胞基因表达调控最关键的环节,其神秘和精深吸引着无数科学家为之奋斗不已。染色质构象捕获及其衍生技术的建立和2003年启动的"DNA元件百科全书"计划,将人们对基因转录调控的认识从二维层面推向三维空间。基因组中分布着众多调控元件,它们与所调控的靶基因间可相距几万甚至几十万个核苷酸,可以与靶基因位于相同或不同的染色体上。依据染色质环模型,调控元件可通过染色质环高级结构,与靶基因在空间上充分接近并相互作用,发挥其调控功能。同一个调控元件可以调控不同的靶基因,而相同的基因亦可能受不同调控元件的调节,由此细胞在染色质高级结构层面形成了一个复杂的调节基因转录活性的三维网络。该文分别从基因远程调控现象的发现、研究方法、相关机制及面临的挑战等方面作一简要综述。

The precise control of gene expression is essential for cell differentiation,individual development and normal life activity of a cell.Transcriptional regulation is a key step to control gene expression in eukaryocyte.The development of chromatin conformation capture（3C） technique with its derived methods and the encyclopedia of DNA elements（ENCODE） project started from 2003 have revealed thousands of putative regulatory elements scattered throughout genome.These regulatory elements are far from their target genes and located either on the chromosome same as their target genes or on the different chromosomes.Transcription of one target gene can be regulated by multiple regulatory elements and one regulatory sequence can also control more than one target genes,which forms a complicated net work at the level of high-ordered chromatin structure.The commonly accepted chromatin loop model is that DNA sequences between enhancers and promoters form loops to allow the distal regulatory sequences to interact directly with the promoters.Here we briefl y review the discovery of long-range regulation of gene expression,development of 3C and the derived techniques,related mechanism involved in longrange regulation and facing challenges within the area.