1. Mammalian SWI/SNF continuously restores local accessibility to chromatin
- Author
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Mario Iurlaro, Francesca Masoni, Giorgio G. Galli, Dirk Schübeler, Michael B. Stadler, and Zainab Jagani
- Subjects
Chromosomal Proteins, Non-Histone ,Protein subunit ,Biology ,Article ,Cell Line ,Histones ,Small Molecule Libraries ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Gene expression ,Genetics ,Nucleosome ,Animals ,Transcription factor ,030304 developmental biology ,Adenosine Triphosphatases ,0303 health sciences ,Binding Sites ,DNA Helicases ,Nuclear Proteins ,Mouse Embryonic Stem Cells ,Chromatin Assembly and Disassembly ,SWI/SNF ,Chromatin ,Cell biology ,DNA-Binding Proteins ,Repressor Proteins ,Gene Expression Regulation ,Receptors, Estrogen ,Regulatory sequence ,Multiprotein Complexes ,ATPases Associated with Diverse Cellular Activities ,Octamer Transcription Factor-3 ,030217 neurology & neurosurgery ,Function (biology) ,Transcription Factors - Abstract
Chromatin accessibility is a hallmark of regulatory regions, entails transcription factor (TF) binding and requires nucleosomal reorganization. However, it remains unclear how dynamic this process is. In the present study, we use small-molecule inhibition of the catalytic subunit of the mouse SWI/SNF remodeler complex to show that accessibility and reduced nucleosome presence at TF-binding sites rely on persistent activity of nucleosome remodelers. Within minutes of remodeler inhibition, accessibility and TF binding decrease. Although this is irrespective of TF function, we show that the activating TF OCT4 (POU5F1) exhibits a faster response than the repressive TF REST. Accessibility, nucleosome depletion and gene expression are rapidly restored on inhibitor removal, suggesting that accessible chromatin is regenerated continuously and in a largely cell-autonomous fashion. We postulate that TF binding to chromatin and remodeler-mediated nucleosomal removal do not represent a stable situation, but instead accessible chromatin reflects an average of a dynamic process under continued renewal.
- Published
- 2020