Regulation of pancreatic microRNA-7 expression.
Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer, which is important for pancreas development. Differentiation of endocrine cells is controlled by a network of pancreatic transcription factors including Ngn3 and NeuroD/Beta2. However, how specific miRNAs are intertwined into this transcriptional network is not well understood. Here, we characterize the regulation of microRNA-7 (miR-7) by endocrine-specific transcription factors. Our data reveal that three independent miR-7 genes are coexpressed in the pancreas. We have identified conserved blocks upstream of pre-miR-7a-2 and pre-miR-7b and demonstrated by functional assays that they possess promoter activity, which is increased by the expression of NeuroD/Beta2. These data suggest that the endocrine specificity of miR-7 expression is governed by transcriptional mechanisms and involves members of the pancreatic endocrine network of transcription factors.
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Sharon
S
Kredo-Russo
Avital
A
Ness
Amitai D
AD
Mandelbaum
Michael D
MD
Walker
Eran
E
Hornstein
D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics*; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012323:RNA Processing, Post-Transcriptional
D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C549242:MIRN7-1 microRNA, human; C498695:NEUROG3 protein, human; C093564:Neurogenic differentiation factor 1