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

Vinod Kumar Yadav,Tapas K Kundu,Akinchan Kumar,Rashi Halder,Shantanu Chowdhury,Bruce Eckloff,Mohammad Parwez Alam,Raj Pandita,Ankita Singh,Ram Krishna Thakur,Aradhita Baral,Tej K Pandita,Eric D Wieben

doi:10.1093/nar/gku596

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.

Highlights

Transcription factors (TFs) can recognize cognate binding sites on the nucleosomal surface, functional binding is almost always associated with chromatin modification, remodeling and displacement or compaction of nucleosomes
Our findings suggest that transcription factor (TF) binding when closely associated with nucleosome repositioning results in altered gene expression changes
In most cases when TF binding did not impact local nucleosome reorganization it was not associated with altered transcriptional state of target gene

Summary

Introduction

Transcription factors (TFs) can recognize cognate binding sites on the nucleosomal surface, functional binding is almost always associated with chromatin modification, remodeling and displacement or compaction of nucleosomes. Though there are several minor variations, the overall chromatin architecture of a given transcription unit may be summarized as: a ‘−1’ nucleosome positioned upstream of the transcription start site (TSS), a nucleosome-free region (NFR) followed by a ‘+1’ nucleosome downstream of TSS, in addition to an array of positioned nucleosomes throughout the gene body [6]. This basic organization is stabilized by modified histones or histone variants placed at specific regions within genes [7,8].

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