Structural Features of Transcription Factors Associating with Nucleosome Binding.

Autor:	Fernandez Garcia M; Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-5157, USA., Moore CD; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Schulz KN; Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI 53706, USA., Alberto O; Institute for Regenerative Medicine, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-5157, USA., Donague G; Institute for Regenerative Medicine, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-5157, USA., Harrison MM; Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin Madison, Madison, WI 53706, USA., Zhu H; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Zaret KS; Institute for Regenerative Medicine, Department of Cell and Developmental Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-5157, USA. Electronic address: zaret@pennmedicine.upenn.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2019 Sep 05; Vol. 75 (5), pp. 921-932.e6. Date of Electronic Publication: 2019 Jul 11.
DOI:	10.1016/j.molcel.2019.06.009
Abstrakt:	Fate-changing transcription factors (TFs) scan chromatin to initiate new genetic programs during cell differentiation and reprogramming. Yet the protein structure domains that allow TFs to target nucleosomal DNA remain unexplored. We screened diverse TFs for binding to nucleosomes containing motif-enriched sequences targeted by pioneer factors in vivo. FOXA1, OCT4, ASCL1/E12α, PU1, CEBPα, and ZELDA display a range of nucleosome binding affinities that correlate with their cell reprogramming potential. We further screened 593 full-length human TFs on protein microarrays against different nucleosome sequences, followed by confirmation in solution, to distinguish among factors that bound nucleosomes, such as the neuronal AP-2α/β/γ, versus factors that only bound free DNA. Structural comparisons of DNA binding domains revealed that efficient nucleosome binders use short anchoring α helices to bind DNA, whereas weak nucleosome binders use unstructured regions and/or β sheets. Thus, specific modes of DNA interaction allow nucleosome scanning that confers pioneer activity to transcription factors. (Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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