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Open Access Research

A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding

Emily Ray Ko, Dennis Ko, Carolyn Chen and Joseph S Lipsick*

Author Affiliations

Departments of Pathology and Genetics, Stanford University School of Medicine, Stanford, CA 94305-5324, USA

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Molecular Cancer 2008, 7:77  doi:10.1186/1476-4598-7-77

Published: 7 October 2008

Abstract

The c-Myb protein is a transcriptional regulator initially identified by homology to the v-Myb oncoprotein, and has since been implicated in human cancer. The most highly conserved portion of the c-Myb protein is the DNA-binding domain which consists of three imperfect repeats. Many other proteins contain one or more Myb-related domains, including a number of proteins that do not bind directly to DNA. We performed a phylogenetic analysis of diverse classes of Myb-related domains and discovered a highly conserved patch of acidic residues common to all Myb-related domains. These acidic residues are positioned in the first of three alpha-helices within each of the three repeats that comprise the c-Myb DNA-binding domain. Interestingly, these conserved acidic residues are present on a surface of the protein which is distinct from that which binds to DNA. Alanine mutagenesis revealed that the acidic patch of the third c-Myb repeat is essential for transcriptional activity, but neither for nuclear localization nor DNA-binding. Instead, these acidic residues are required for efficient chromatin binding and interaction with the histone H4 N-terminal tail.