Nucleosome organization in the vicinity of transcription factor binding sites in the human genome

BMC Genomics

Xiao Sun¹  Jiao Chen¹  Xiangfei Cheng¹  Yumin Nie¹ 

[1] State Key Laboratory of Bioelectronics, School of Biological Science & Medical Engineering, Southeast University, 210096 Nanjing, China

关键词: Clustering;    Transcription factor binding site;    Nucleosome occupancy;   

Others  :  857099
DOI  :  10.1186/1471-2164-15-493

 received in 2013-12-24, accepted in 2014-06-10,  发布年份 2014

【 摘 要 】

Background

The binding of transcription factors (TFs) to specific DNA sequences is an initial and crucial step of transcription. In eukaryotes, this process is highly dependent on the local chromatin state, which can be modified by recruiting chromatin remodelers. However, previous studies have focused mainly on nucleosome occupancy around the TF binding sites (TFBSs) of a few specific TFs. Here, we investigated the nucleosome occupancy profiles around computationally inferred binding sites, based on 519 TF binding motifs, in human GM12878 and K562 cells.

Results

Although high nucleosome occupancy is intrinsically encoded at TFBSs in vitro, nucleosomes are generally depleted at TFBSs in vivo, and approximately a quarter of TFBSs showed well-positioned in vivo nucleosomes on both sides. RNA polymerase near the transcription start site (TSS) has a large effect on the nucleosome occupancy distribution around the binding sites located within one kilobase to the nearest TSS; fuzzier nucleosome positioning was thus observed around these sites. In addition, in contrast to yeast, repressors, rather than activators, were more likely to bind to nucleosomal DNA in the human cells, and nucleosomes around repressor sites were better positioned in vivo. Genes with repressor sites exhibiting well-positioned nucleosomes on both sides, and genes with activator sites occupied by nucleosomes had significantly lower expression, suggesting that actions of activators and repressors are associated with the nucleosome occupancy around their binding sites. It was also interesting to note that most of the binding sites, which were not in the DNase I-hypersensitive regions, were cell-type specific, and higher in vivo nucleosome occupancy were observed at these binding sites.

Conclusions

This study demonstrated that RNA polymerase and the functions of bound TFs affected the local nucleosome occupancy around TFBSs, and nucleosome occupancy patterns around TFBSs were associated with the expression levels of target genes.

【 授权许可】

   
2014 Nie et al.; licensee BioMed Central Ltd.

【 图 表 】

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