Fig. 2

MicroRNA-promoter interaction mechanisms. There are three models for microRNA-promoter interaction, all of which underscore the importance of Ago protein, though there are some conflicting views on whether Ago1 or Ago2 is involved. The resultant interaction effect can be either transcriptional activation or transcriptional suppression. In most cases, the RNA-DNA and the RNA-RNA hybrid model rely on histone modifiers and the recruitment of RNA polymerase II, while whether microRNA can mediate DNA methylation remains dubious. Moreover, in the RNA-DNA-DNA triplex model, the interaction is not related to epigenetic modification. a In the RNA-DNA model, microRNA-Ago complex directly targets to one of the DNA strands which always contains the TATA box motif or transcription factor binding sites when this region is in open configuration for transcription. Then some transcription factors and/or epigenetic modifiers are recruited to the promoter region leading to RNA polymerase II recruitment and/or epigenetic modification. b The RNA-RNA model is related to the non-coding transcripts derived from the promoter region. Either sense or antisense transcript can be a target for microRNA-Ago complex, serving as a scaffold for microRNA-Ago complex and recruiting the histone modifiers and/or transcription factors. c In the RNA-DNA triplex model, microRNAs form triple-helical structures with DNA, altering the topography of the chromatin, which is rendered either more accessible or inaccessible to distinct transcription factors. TF, transcription factor; ncRNA, non-coding RNA; RNA pol II, RNA polymerase II; TSS, transcription start site; Ago, Argonaute 1 or Argonaute 2; Histone modifiers, such as histone methyltransferase enhancer of zeste homolog 2 (EZH2) and euchromatic histone lysine methyltransferase 2 (EHMT2)