Genome-wide survey of tissue-specific microRNA and transcription factor regulatory networks in 12 tissues.

Zhiyun Guo,Ruofan Ding,Lili Xiong,Bao Zhang,Yalan Yang,Miranda Maki

doi:10.1038/srep05150

Zhiyun Guo, Ruofan Ding + Show 4 more

Open Access

https://doi.org/10.1038/srep05150

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Abstract

Tissue-specific miRNAs (TS miRNA) specifically expressed in particular tissues play an important role in tissue identity, differentiation and function. However, transcription factor (TF) and TS miRNA regulatory networks across multiple tissues have not been systematically studied. Here, we manually extracted 116 TS miRNAs and systematically investigated the regulatory network of TF-TS miRNA in 12 human tissues. We identified 2,347 TF-TS miRNA regulatory relations and revealed that most TF binding sites tend to enrich close to the transcription start site of TS miRNAs. Furthermore, we found TS miRNAs were regulated widely by non-tissue specific TFs and the tissue-specific expression level of TF have a close relationship with TF-genes regulation. Finally, we describe TSmiR (http://bioeng.swjtu.edu.cn/TSmiR), a novel and web-searchable database that houses interaction maps of TF-TS miRNA in 12 tissues. Taken together, these observations provide a new suggestion to better understand the regulatory network and mechanisms of TF-TS miRNAs underlying different tissues.

Highlights

Tissue-specific miRNAs (TS miRNA) expressed in particular tissues play an important role in tissue identity, differentiation and function
We found TS miRNAs were regulated widely by non-tissue specific transcription factor (TF) and the tissue-specific expression level of TF have a close relationship with TFgenes regulation
Through the integration of TF expression data, we found that tissue-specific miRNAs were regulated widely by nontissue specific TFs

Summary

Heart Skeletal muscle Lung Bone Kidney Liver Placenta

Spleen Thymus Pancreas miR-1, miR-126, miR-208, miR-302a, miR-302b, miR-302c, miR-302d, miR-367, miR-133a, miR-133b miR-1, miR-206, miR-134, miR-193a, miR-128a, miR-133a, miR-133b, miR-95, miR-208a miR-126 miR-483, miR-377, miR-92a miR-200a, miR-196a, miR-196b, miR-10a, miR-10b, miR-146a, miR-30c, miR-204 miR-122, miR-483, miR-92a, miR-192 miR-377, miR-498, miR-527, miR-526a, miR-526b, miR-184, miR-154, miR-381, miR-503, miR-373, miR-371, miR-372, miR-519a, miR-519b, miR-519c, miR-519d, miR-519e, miR-516b, miR-520a, miR-520b, miR-520c, miR-520d, miR-520e, miR-520f, miR-520g, miR-520h, miR-517a, miR-517b, miR-517c, miR-450, miR-518a, miR-518b, miR-518c, miR-518d, miR-518e, miR-518f, miR-522, miR-524, miR-521, miR-523, miR-525, miR-512, miR-136. A series of TF-TS miRNA regulatory networks presented here, revealing that TF-gene regulatory relationships in network displayed two distinct types: type I : The highly tissue-specific or widely expressed TFs make less intensive interactions than other TFs; and type II: tissue-specific TFs participate in more interactions than other non-specific expression TFs. the TSmiR database was presented here (http:// bioeng.swjtu.edu.cn/TSmiR) to provide interaction maps and expression data of transcription factor and tissue-specific miRNAs in 12 tissues. The TSmiR database was presented here (http:// bioeng.swjtu.edu.cn/TSmiR) to provide interaction maps and expression data of transcription factor and tissue-specific miRNAs in 12 tissues To our knowledge, this is the first systematic attempt to construct a regulatory network of tissue-specific miRNAs across multiple tissues, which can help to elucidate the molecular mechanisms of tissue-specific miRNAs network in tissue development and function

Results and discussion

Lung thymus Spleen

Skeletal muscle

Methods

Additional information