Interaction of the myogenic determination factor myogenin with E12 and a DNA target: mechanism and kinetics

Journal of Molecular Biology
Daryl S SpinnerJakob Schmidt

Abstract

The myogenic determination factors MyoD, myogenin, myf5, and MRF4 are members of the basic helix-loop-helix (bHLH) family of transcription factors and crucial agents of myogenesis. The bHLH regions of these proteins enable them to dimerize with E proteins, another class of the bHLH family, and to bind a specific DNA element known as an E box (CANNTG consensus sequence), which results in the activation of muscle-specific gene expression. As a model for such assembly of the myogenic determination factor/E protein-DNA ternary complex, we have studied the physiologically relevant association of myogenin, E12, and the 3' E box of the acetylcholine receptor (AChR) alpha-subunit gene enhancer. Using the technique of electrophoretic mobility shift assay combined with order-of-addition and time-course experiments, we find that heterodimerization of myogenin with E12 occurs prior to DNA-binding. In addition, we deduce the dissociation (Kd) and rate (k) constants for each step in the formation of the myogenin/E12-DNA ternary complex. Kinetic simulations indicate that at 37 degrees C myogenin and E12 heterodimerize with a Kd of 36 microM (k(on) of 573 M(-1) x s(-1) and k(off )of 0.0205 x s(-1)), and that subsequently the heterodimer binds ...Continue Reading

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Citations

Jun 21, 2005·Molecular and Cellular Biology·Chang-Hoon KimLin Mei
Jul 29, 2009·EURASIP Journal on Bioinformatics & Systems Biology·Zhouyi Xu, Xiaodong Cai
Aug 23, 2012·PLoS Biology·Christian SchröterAndrew C Oates
Aug 16, 2015·Biology Direct·Reiner A Veitia, James A Birchler
May 24, 2007·The Journal of Biological Chemistry·Mónica Martínez-MorenoIgnacio Rodríguez-Crespo
Feb 9, 2020·International Journal of Molecular Sciences·Kiyoto KamagataDwiky Rendra Graha Subekti
May 11, 2016·Proceedings of the National Academy of Sciences of the United States of America·Javier Muñoz-García, Saúl Ares
Jan 16, 2007·Science·Sebastian J Maerkl, Stephen R Quake
Sep 14, 2010·Current Opinion in Biotechnology·Sebastian J Maerkl

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