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Promoter-proximal transcription factor binding is transcriptionally active when coupled with nucleosome repositioning in immediate vicinity.

ABSTRACT: Previous studies have analyzed patterns of transcription, transcription factor (TF) binding or mapped nucleosome occupancy across the genome. These suggest that the three aspects are genetically connected but the cause and effect relationships are still unknown. For example, physiologic TF binding studies involve many TFs, consequently, it is difficult to assign nucleosome reorganization to the binding site occupancy of any particular TF. Therefore, several aspects remain unclear: does TF binding influence nucleosome (re)organizations locally or impact the chromatin landscape at a more global level; are all or only a fraction of TF binding a result of reorganization in nucleosome occupancy and do all TF binding and associated changes in nucleosome occupancy result in altered gene expression? With these in mind, following characterization of two states (before and after induction of a single TF of choice) we determined: (i) genomic binding sites of the TF, (ii) promoter nucleosome occupancy and (iii) transcriptome profiles. Results demonstrated that promoter-proximal TF binding influenced expression of the target gene when it was coupled to nucleosome repositioning at or close to its binding site in most cases. In contrast, only in few cases change in target gene expression was found when TF binding occurred without local nucleosome reorganization.

SUBMITTER: Yadav VK

PROVIDER: S-EPMC4150765 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Promoter-proximal transcription factor binding is transcriptionally active when coupled with nucleosome repositioning in immediate vicinity.

Yadav Vinod Kumar VK Thakur Ram Krishna RK Eckloff Bruce B Baral Aradhita A Singh Ankita A Halder Rashi R Kumar Akinchan A Alam Mohammad Parwez MP Kundu Tapas K TK Pandita Raj R Pandita Tej K TK Wieben Eric D ED Chowdhury Shantanu S

Nucleic acids research 20140731 15

Previous studies have analyzed patterns of transcription, transcription factor (TF) binding or mapped nucleosome occupancy across the genome. These suggest that the three aspects are genetically connected but the cause and effect relationships are still unknown. For example, physiologic TF binding studies involve many TFs, consequently, it is difficult to assign nucleosome reorganization to the binding site occupancy of any particular TF. Therefore, several aspects remain unclear: does TF bindin ...[more]

PMID: 25081206

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Project description:BackgroundThe 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.ResultsAlthough 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.ConclusionsThis 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.

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Promoter-proximal transcription factor binding is transcriptionally active when coupled with nucleosome repositioning in immediate vicinity.

Publications

Promoter-proximal transcription factor binding is transcriptionally active when coupled with nucleosome repositioning in immediate vicinity.

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