GSBS Student to be published in the Journal of Biological Chemistry
GSBS student Joshua Boucher will have his first 1st author publication in the Journal of Biological Chemistry. The article, entitled “THE miR-143/145 CLUSTER IS A NOVEL TRANSCRIPTIONAL TARGET OF JAGGED-1/NOTCH SIGNALING IN VASCULAR SMOOTH MUSCLE CELLS” will apear in the journal’s August edition. Congratulations, Josh! An abstract is provided below for more information.
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Abstract:
THE miR-143/145 CLUSTER IS A NOVEL TRANSCRIPTIONAL TARGET OF JAGGED-1/NOTCH SIGNALING IN VASCULAR SMOOTH MUSCLE CELLS
Joshua M. Boucher1,2, B.S., Sarah M. Peterson1,2, M.D., Sumithra Urs1, Ph.D., Chunxiang Zhang, M.D., Ph.D3., and Lucy Liaw1,2, Ph.D.*
1 The Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, ME 04074;
2The Graduate School of Biomedical Sciences, University of Maine, Orono, ME 04473; and
3 Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07101
Running Head: miR-143/145 is a novel Jagged-1/Notch target
Address correspondence to: Lucy Liaw, Ph.D., Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074 Tel: 207-396-8142; Fax: 207-396-8179; Email liawl@mmc.org
Activation of Notch signaling by Jagged-1 (Jag-1)1 in vascular smooth muscle cells (VSMC) promotes a differentiated phenotype characterized by increased expression of contractile proteins. Recent studies show that microRNAs (miR)-143/145 regulates VSMC phenotype. The serum response factor (SRF)/myocardin complex binds to CArG sequences to activate miR-143/145 transcription, but no other regulators are known in VSMC. Using miR arrays, we found miR-143/145 induced following expression of a constitutively active Notch1 intracellular domain (N1ICD). We hypothesized that miR-143/145 is required for Jag-1/Notch induced VSMC differentiation. Activation of Notch receptors by Jag-1 caused CBF1-dependent upregulation of miR-143/145, increased differentiation, and decreased proliferation. Conversely, inhibiting basal Notch signaling decreased steady state levels of miR-143/145. Using SRF knockdown, we found that Jag-1/Notch induction of miR-143/145 is SRF independent, although full acquisition of contractile markers requires SRF. Using miR-143/145 promoter reporter constructs we show Jag-1/Notch increases promoter activity, and this is dependent on intact CBF1 consensus sites within the promoter. Chromatin immunoprecipitation (ChIP) assays revealed that N1ICD-containing complexes bind to