Transcriptional activation of the insulin-like growth factor-II gene during myoblast differentiation

Molecular Endocrinology
K Kou, Peter Rotwein

Abstract

Insulin-like growth factor-II (IGF-II) is a secreted 67-amino acid peptide that functions principally as a prenatal growth regulator in mammals. To date, the mechanisms involved in the stimulation of IGF-II expression in the embryo and its attenuation after birth are unknown. Recent studies have shown that IGF-II mRNA and protein are induced during the terminal stages of muscle development in vitro, and that IGF-II may act as an autocrine differentiation agent for skeletal myoblasts. We now have investigated the regulation of IGF-II gene expression in muscle cells. Steady state levels of IGF-II mRNA increased by more than 30-fold during terminal differentiation of the C2 mouse myoblast cell line. Transcription run-on experiments using isolated muscle cell nuclei and direct analysis of nuclear RNA each demonstrated a greater than 10-fold rise in nascent IGF-II mRNA during cellular differentiation, and ribonuclease protection experiments showed that more than 95% of IGF-II mRNAs initiated in noncoding exon 3, implying that transcriptional activation occurs principally through promoter 3, the most 3' of the three mouse IGF-II gene promoters. Analysis of chromatin structure around the IGF-II gene in C2 cells revealed four major and...Continue Reading

Citations

Apr 16, 2011·Journal of Medicinal Chemistry·Debora EspositoIlya Raskin
Oct 13, 2010·The Journal of Biological Chemistry·Damir T AlzhanovPeter Rotwein
Nov 26, 2010·Molecular Endocrinology·Samantha GardnerPeter Rotwein
Aug 8, 2015·Molecular and Cellular Endocrinology·Sarbani SahaRupasri Ain

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