Structural Basis for DNA Recognition by FOXC2

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2019 Feb 6

PMID 30722065

Citations 25

Authors

Xiaojuan Chen

Hudie Wei

Jun Li

Xujun Liang

Shuyan Dai

Longying Jiang

Ming Guo

Lingzhi Qu

Zhuchu Chen

Lin Chen

Yongheng Chen

Affiliations

Soon will be listed here.

Abstract

The FOXC family of transcription factors (FOXC1 and FOXC2) plays essential roles in the regulation of embryonic, ocular, and cardiac development. Mutations and abnormal expression of FOXC proteins are implicated in genetic diseases as well as cancer. In this study, we determined two crystal structures of the DNA-binding domain (DBD) of human FOXC2 protein, in complex with different DNA sites. The FOXC2-DBD adopts the winged-helix fold with helix H3 contributing to all the base specific contacts, while the N-terminus, wing 1, and the C-terminus of FOXC2-DBD all make additional contacts with the phosphate groups of DNA. Our structural, biochemical, and bioinformatics analyses allow us to revise the previously proposed DNA recognition mechanism and provide a model of DNA binding for the FOXC proteins. In addition, our structural analysis and accompanying biochemical assays provide a molecular basis for understanding disease-causing mutations in FOXC1 and FOXC2.

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