Mar 15, 2016

Modeling methyl-sensitive transcription factor motifs with an expanded epigenetic alphabet

BioRxiv : the Preprint Server for Biology
Coby VinerMichael M. Hoffman

Abstract

Introduction. Many transcription factors initiate transcription only in specific sequence contexts, providing the means for sequence specificity of transcriptional control. A four-letter DNA alphabet only partially describes the possible diversity of nucleobases a transcription factor might encounter. For instance, cytosine is often present in a covalently modified form: 5-methylcytosine (5mC). 5mC can be successively oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Just as transcription factors distinguish one unmodified nucleobase from another, some have been shown to distinguish unmodified bases from these covalently modified bases. Modification-sensitive transcription factors provide a mechanism by which widespread changes in DNA methylation and hydroxymethylation can dramatically shift active gene expression programs. Methods. To understand the effect of modified nucleobases on gene regulation, we developed methods to discover motifs and identify transcription factor binding sites in DNA with covalent modifications. Our models expand the standard A/C/G/T alphabet, adding m (5mC) h (5hmC), f (5fC), and c (5caC). We additionally add symbols to encode guanine complementary to ...Continue Reading

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Mentioned in this Paper

Guanine
In Vivo
Covalent Interaction
Transcriptional Regulation
T-Lymphocyte
MYC protein, human
Alphabet protein, Drosophila
Protein Methylation
Genome
Transcription, Genetic

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