Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor

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Title: Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor
Authors: Liu, Yubing
Nandi, Soumyadeep
Martel, André
Antoun, Alen
Ioshikhes, Ilya
Blais, Alexandre
Date: 2012
Abstract: The Six1 transcription factor is a homeodomain protein involved in controlling gene expression during embryonic development. Six1 establishes gene expression profiles that enable skeletal myogenesis and nephrogenesis, among others. While several homeodomain factors have been extensively characterized with regards to their DNA-binding properties, relatively little is known of the properties of Six1. We have used the genomic binding profile of Six1 during the myogenic differentiation of myoblasts to obtain a better understanding of its preferences for recognizing certain DNA sequences. DNA sequence analyses on our genomic binding dataset, combined with biochemical characterization using binding assays, reveal that Six1 has a much broader DNA-binding sequence spectrum than had been previously determined. Moreover, using a position weight matrix optimization algorithm, we generated a highly sensitive and specific matrix that can be used to predict novel Six1-binding sites with highest accuracy. Furthermore, our results support the idea of a mode of DNA recognition by this factor where Six1 itself is sufficient for sequence discrimination, and where Six1 domains outside of its homeodomain contribute to binding site selection. Together, our results provide new light on the properties of this important transcription factor, and will enable more accurate modeling of Six1 function in bioinformatic studies.
URL: http://hdl.handle.net/10393/24229
http://nar.oxfordjournals.org/content/40/17/8227.long
DOI: 10.1093/nar/gks587
CollectionBiochimie, microbiologie et immunologie // Biochemistry, Microbiology and Immunology
Libre accès uOttawa - Publications // uOttawa Open Access - Publications
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