Kim Aeri, Zhao Hui, Ifrim Ina, Dean Ann
Laboratory of Cellular and Developmental Biology, NIDDK, NIH, Bethesda, MD 20892, USA.
Mol Cell Biol. 2007 Apr;27(8):2980-6. doi: 10.1128/MCB.02337-06. Epub 2007 Feb 5.
Histone acetyltransferases are associated with the elongating RNA polymerase II (Pol II) complex, supporting the idea that histone acetylation and transcription are intertwined mechanistically in gene coding sequences. Here, we studied the establishment and function of histone acetylation and transcription in noncoding sequences by using a model locus linking the beta-globin HS2 enhancer and the embryonic epsilon-globin gene in chromatin. An intact HS2 enhancer that recruits RNA Pol II is required for intergenic transcription and histone H3 acetylation and K4 methylation between the enhancer and target gene. RNA Pol II recruitment to the target gene TATA box is not required for the intergenic transcription or intergenic histone modifications, strongly implying that they are properties conferred by the enhancer. However, Pol II recruitment at HS2, intergenic transcription, and intergenic histone modification are not sufficient for transcription or modification of the target gene: these changes require initiation at the TATA box of the gene. The results suggest that intergenic and genic transcription complexes are independent and possibly differ from one another.
组蛋白乙酰转移酶与延伸中的RNA聚合酶II(Pol II)复合物相关,这支持了组蛋白乙酰化和转录在基因编码序列中存在机制上的交织这一观点。在此,我们通过使用一个将β-珠蛋白HS2增强子与染色质中的胚胎ε-珠蛋白基因相连的模型位点,研究了非编码序列中组蛋白乙酰化和转录的建立及功能。一个完整的、能招募RNA Pol II的HS2增强子对于基因间转录以及增强子与靶基因之间的组蛋白H3乙酰化和K4甲基化是必需的。基因间转录或基因间组蛋白修饰并不需要RNA Pol II招募到靶基因的TATA框,这强烈暗示它们是由增强子赋予的特性。然而,HS2处的Pol II招募、基因间转录和基因间组蛋白修饰对于靶基因的转录或修饰并不充分:这些变化需要在基因的TATA框处起始。结果表明基因间和基因转录复合物是独立的,且可能彼此不同。