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Nucleosomes inhibit intragenic binding of Rap1p and subsequent cryptic transcription

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE92468 | GEO | 2021/11/01

REPOSITORIES: GEO

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Nucleosomes inhibit intragenic binding of Rap1p and subsequent cryptic transcription [ChIP-seq]

Project description:Nucleosomes are the primary unit of chromatin structure and inhibit key intracellular interactions which regulate how eukaryotic genetic information is read, including transcription factor (TF) binding to DNA. In theory, the sterics of nucleosome-DNA interactions could inhibit TF binding to all nucleosome-bound DNA. In reality, however, nucleosome inhibition of TF binding is variable both across a genome and even within a single nucleosome. Prior studies have demonstrated that nucleosome occupancy, nucleosome positioning, TF binding site (TFBS) affinity & TFBS location can each influence TF targeting in vivo, however, this work has been largely correlative and no study has dissected collective from individual contributions of these important variables. Therefore, to address this deficiency, we have mapped genome-wide changes in chromatin structure and TF binding following experimental nucleosome depletion. Heuristic modeling of results confirmed that chromatin specification of TF targeting is a multivariate, context-specific, process, with most informative features originating from additive interactions between cis and trans variables. Additionally, we found compelling evidence that nucleosomes serve to inhibit intra-genic TF binding, as evidenced by an increasing number of sub-optimal TFBS occupied following nucleosome depletion. The majority of these conditional loci were located within open reading frames and parallel transcriptome analysis revealed their occurrence was linked to generation of intragenic cryptic transcripts. Together results support the idea that chromatin structure has evolved to coordinate specification of regulatory factor targeting & gene expression. Findings have functional relevance to emerging datasets on genetic and epigenetic variation in human disease states.

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Nucleosomes inhibit intragenic binding of Rap1p and subsequent cryptic transcription

Project description:Nucleosomes inhibit intragenic binding of Rap1p and subsequent cryptic transcription

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