title: Defining Transcriptional Regulatory Mechanisms for Primary let-7 miRNAs.
abstract: The let-7 family of miRNAs have been shown to control developmental timing in organisms from C. elegans to humans; their function in several essential cell processes throughout development is also well conserved. Numerous studies have defined several steps of post-transcriptional regulation of let-7 production; from pri-miRNA through pre-miRNA, to the mature miRNA that targets endogenous mRNAs for degradation or translational inhibition. Less-well defined are modes of transcriptional regulation of the pri-miRNAs for let-7. let-7 pri-miRNAs are expressed in polycistronic fashion, in long transcripts newly annotated based on chromatin-associated RNA-sequencing. Upon differentiation, we found that some let-7 pri-miRNAs are regulated at the transcriptional level, while others appear to be constitutively transcribed. Using the Epigenetic Roadmap database, we further annotated regulatory elements of each polycistron identified putative promoters and enhancers. Probing these regulatory elements for transcription factor binding sites identified factors that regulate transcription of let-7 in both promoter and enhancer regions, and identified novel regulatory mechanisms for this important class of miRNAs.
authors.affiliation: Broad Stem Cell Center, University of California Los Angeles, Los Angeles, California, United States of America.|Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gaeta
authors.affiliation: Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Luat
authors.initials: L
authors.lastname: Le
authors.affiliation: Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Broad Stem Cell Center, University of California Los Angeles, Los Angeles, California, United States of America.|Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America.|Molecular, Cell and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America.|Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: William E
authors.initials: WE
authors.lastname: Lowry
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human