On 2017 Apr 23, Wenqiang Yu commented:

My comments on this impressive paper are mainly regarding the relationship between the enhancer and microRNA. MicroRNAs are expressed in a tissue and cell type specific manner, as is the enhancer. Therefore, it would be intriguing to know whether miRNA and enhancer may be intrinsically linked while regulating gene expression. Results of this paper are interesting because Suzuki HI et al found that enhancer regions overlap with miRNA genome loci and may play a role in shaping the tissue-specific gene expression pattern. These findings directly support our earlier results from a 5-year long project that was finally published in RNA biology in the beginning of 2016, “MicroRNAs Activate Gene Transcription Epigenetically as an Enhancer Trigger”.(http://www.tandfonline.com/doi/abs/10.1080/15476286.2015.1112487?journalCode=krnb20) In this paper, we not only found that many miRNA genome loci overlap with enhancer regions, but also identified a subset of miRNAs in the nucleus that function as universal and natural gene activators emanating from the enhancer loci, which we termed NamiRNA (Nuclear activating miRNA; although this specific term was not used in the paper). These miRNAs are associated with active enhancers characterized by distinct H3K27ac enrichment, p300/CBP binding and DNase I hypersensitivity. We also presented evidence that NamiRNA promotes genome-wide gene transcription through the binding and activating of its targeted enhancers. Thus, we anticipate that NamiRNA-enhancer-mRNA activation network may be involved in cell behavior modulation during development and disease progression. Having said all that, we hope our results published in RNA biology can be cited by this paper. Meanwhile, we want to emphasize the dual functionality of miRNAs that is supported by our results---work as an activator via enhancer in the nucleus and as a traditional silencer in the cytoplasm. In light of this, more attention should be paid towards research that clarifies the detail of these NamiRNAs functions. It is in our belief that the miRNA-enhancer-gene activation network may be the intrinsic link between miRNA and enhancer when the two coordinate in regulating gene expression during cell fate transitions.

On 2017 Apr 23, Wenqiang Yu commented:

My comments on this impressive paper are mainly regarding the relationship between the enhancer and microRNA. MicroRNAs are expressed in a tissue and cell type specific manner, as is the enhancer. Therefore, it would be intriguing to know whether miRNA and enhancer may be intrinsically linked while regulating gene expression. Results of this paper are interesting because Suzuki HI et al found that enhancer regions overlap with miRNA genome loci and may play a role in shaping the tissue-specific gene expression pattern. These findings directly support our earlier results from a 5-year long project that was finally published in RNA biology in the beginning of 2016, “MicroRNAs Activate Gene Transcription Epigenetically as an Enhancer Trigger”.(http://www.tandfonline.com/doi/abs/10.1080/15476286.2015.1112487?journalCode=krnb20) In this paper, we not only found that many miRNA genome loci overlap with enhancer regions, but also identified a subset of miRNAs in the nucleus that function as universal and natural gene activators emanating from the enhancer loci, which we termed NamiRNA (Nuclear activating miRNA; although this specific term was not used in the paper). These miRNAs are associated with active enhancers characterized by distinct H3K27ac enrichment, p300/CBP binding and DNase I hypersensitivity. We also presented evidence that NamiRNA promotes genome-wide gene transcription through the binding and activating of its targeted enhancers. Thus, we anticipate that NamiRNA-enhancer-mRNA activation network may be involved in cell behavior modulation during development and disease progression. Having said all that, we hope our results published in RNA biology can be cited by this paper. Meanwhile, we want to emphasize the dual functionality of miRNAs that is supported by our results---work as an activator via enhancer in the nucleus and as a traditional silencer in the cytoplasm. In light of this, more attention should be paid towards research that clarifies the detail of these NamiRNAs functions. It is in our belief that the miRNA-enhancer-gene activation network may be the intrinsic link between miRNA and enhancer when the two coordinate in regulating gene expression during cell fate transitions.