cooperativity of stress-responsive transcription factors in core hypoxia-inducible factor binding regions核心低氧诱导因子协同逆境应答的转录因子的结合区域.pdf

Cooperativity of Stress-Responsive Transcription Factors in Core Hypoxia-Inducible Factor Binding Regions 1 ¤ 1 ´ 1 1 ´ ´ Diego Villar * , Amaya Ortiz-Barahona , Laura Gomez-Maldonado , Nuria Pescador , Fatima Sanchez- 2 3 4 3 2 4 Cabo , Hubert Hackl , Benjamin A. T. Rodriguez , Zlatko Trajanoski , Ana Dopazo , Tim H. M. Huang , Pearlly S. Yan4, Luis del Peso1 ´ 1 Department of Biochemistry, Universidad Autonoma de Madrid and Instituto de Investigaciones Biomedicas Alberto Sols, Madrid, Spain, 2 Genomics Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain, 3 Biocenter, Division of Bioinformatics, Innsbruck Medical University, Innsbruck, Austria, 4 Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, Ohio, United States of America Abstract The transcriptional response driven by Hypoxia-inducible factor (HIF) is central to the adaptation to oxygen restriction. Despite recent characterization of genome-wide HIF DNA binding locations and hypoxia-regulated transcripts in different cell types, the molecular bases of HIF target selection remain unresolved. Herein, we combined multi-level experimental data and computational predictions to identify sequence motifs that may contribute to HIF target selectivity. We obtained a core set of bona fide HIF binding regions by integrating multiple HIF1 DNA binding and hypoxia expression profiling datasets. This core set exhibits evolutionarily conser