Comprehensive characterization of erythroid-specific enhancers in the genomic regions of human Krüppel-like factors

BMC Genomics

Research Article

Yaran Yang¹  Xiuyan Ruan¹  Yajuan Li¹  Zhaojun Zhang¹  Yadong Yang¹  Hongzhu Qu²  Xiangdong Fang³  Heyuan Qi⁴  Qian Xiong⁴  Yanming Li⁴  Hai Wang⁵  Richard Sandstrom⁶  Peter J Sabo⁶  John A Stamatoyannopoulos⁶  Kai-Hsin Chang⁷  George Stamatoyannopoulos⁸  Qiliang Li⁸ 

[1] CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, P.R. China;CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, P.R. China;Department of Genome Sciences, University of Washington, 98195, Seattle, WA, USA;CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, P.R. China;Division of Medical Genetics, Department of Medicine, University of Washington, 98195, Seattle, WA, USA;CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, P.R. China;University of Chinese Academy of Sciences, 100049, Beijing, P.R. China;CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101, Beijing, P.R. China;University of Chinese Academy of Sciences, 100049, Beijing, P.R. China;Division of Hematology, Department of Medicine, University of Washington, 98195, Seattle, WA, USA;Department of Genome Sciences, University of Washington, 98195, Seattle, WA, USA;Division of Hematology, Department of Medicine, University of Washington, 98195, Seattle, WA, USA;Division of Medical Genetics, Department of Medicine, University of Washington, 98195, Seattle, WA, USA;

关键词: DHS profiling;    High-throughput sequencing;    Erythroid;    Enhancer;    Krüppel-like factors;   

DOI  :  10.1186/1471-2164-14-587

 received in 2013-03-18, accepted in 2013-08-23,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundMapping of DNase I hypersensitive sites (DHSs) is a powerful tool to experimentally identify cis-regulatory elements (CREs). Among CREs, enhancers are abundant and predominantly act in driving cell-specific gene expression. Krüppel-like factors (KLFs) are a family of eukaryotic transcription factors. Several KLFs have been demonstrated to play important roles in hematopoiesis. However, transcriptional regulation of KLFs via CREs, particularly enhancers, in erythroid cells has been poorly understood.ResultsIn this study, 23 erythroid-specific or putative erythroid-specific DHSs were identified by DNase-seq in the genomic regions of 17 human KLFs, and their enhancer activities were evaluated using dual-luciferase reporter (DLR) assay. Of the 23 erythroid-specific DHSs, the enhancer activities of 15 DHSs were comparable to that of the classical enhancer HS2 in driving minimal promoter (minP). Fifteen DHSs, some overlapping those that increased minP activities, acted as enhancers when driving the corresponding KLF promoters (KLF-Ps) in erythroid cells; of these, 10 DHSs were finally characterized as erythroid-specific KLF enhancers. These 10 erythroid-specific KLF enhancers were further confirmed using chromatin immunoprecipitation coupled to sequencing (ChIP-seq) data-based bioinformatic and biochemical analyses.ConclusionOur present findings provide a feasible strategy to extensively identify gene- and cell-specific enhancers from DHSs obtained by high-throughput sequencing, which will help reveal the transcriptional regulation and biological functions of genes in some specific cells.

【 授权许可】

Unknown   
© Xiong et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.