title: Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail.
abstract: ISWI-family nucleosome remodeling enzymes need the histone H4 N-terminal tail to mobilize nucleosomes. Here we mapped the H4-tail binding pocket of ISWI. Surprisingly the binding site was adjacent to but not overlapping with the docking site of an auto-regulatory motif, AutoN, in the N-terminal region (NTR) of ISWI, indicating that AutoN does not act as a simple pseudosubstrate as suggested previously. Rather, AutoN cooperated with a hitherto uncharacterized motif, termed AcidicN, to confer H4-tail sensitivity and discriminate between DNA and nucleosomes. A third motif in the NTR, ppHSA, was functionally required in vivo and provided structural stability by clamping the NTR to Lobe 2 of the ATPase domain. This configuration is reminiscent of Chd1 even though Chd1 contains an unrelated NTR. Our results shed light on the intricate structural and functional regulation of ISWI by the NTR and uncover surprising parallels with Chd1.
authors.affiliation: Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Ludwigsen
authors.affiliation: Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Pfennig
authors.affiliation: Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Physics Department (T38), Technische Universität München, Munich, Germany.|Center for Integrated Protein Science Munich, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Schindler
authors.affiliation: Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Harrer
authors.affiliation: Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Forné
authors.affiliation: Physics Department (T38), Technische Universität München, Munich, Germany.|Center for Integrated Protein Science Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
authors.affiliation: Biomedical Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Felix
authors.identifier: 0000-0001-8273-6473
authors.initials: F
authors.lastname: Mueller-Planitz
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D004330:Drosophila; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; C086468:ISWI protein; D014157:Transcription Factors; D000251:Adenosine Triphosphatases
keywords: ATPase; S. cerevisiae; Snf2; biochemistry; chromatin remodeling; chromosomes; genes; nucleosome