Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail

• Published in: eLife 2017-01, Vol.6
• Main Authors: Ludwigsen, Johanna, Pfennig, Sabrina, Singh, Ashish K, Schindler, Christina, Harrer, Nadine, Forné, Ignasi, Zacharias, Martin, Mueller-Planitz, Felix
• Format: Article
• Language: English
• Subjects: Adenosine triphosphatase; Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Amino Acid Motifs; Amino acids; Animals; ATPase; Binding sites; Biochemistry; chromatin remodeling; Deoxyribonucleic acid; DNA; Drosophila; Enzyme kinetics; Gene Expression Regulation; Genes and Chromosomes; Histone H4; Histones; Histones - metabolism; Mass spectrometry; Mutation; nucleosome; Nucleosomes; Observations; Peptides; Physiological aspects; Protein Binding; Protein Interaction Mapping; Proteins; Saccharomyces cerevisiae; Scientific imaging; Snf2; Structure-function relationships; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.21477

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.