Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail
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 regi...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2017-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/21477 |
| _version_ | 1811180584105410560 |
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| author | Johanna Ludwigsen Sabrina Pfennig Ashish K Singh Christina Schindler Nadine Harrer Ignasi Forné Martin Zacharias Felix Mueller-Planitz |
| author_facet | Johanna Ludwigsen Sabrina Pfennig Ashish K Singh Christina Schindler Nadine Harrer Ignasi Forné Martin Zacharias Felix Mueller-Planitz |
| author_sort | Johanna Ludwigsen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:05:37Z |
| format | Article |
| id | doaj.art-ff843e54053a417491a69848ba66e7b3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:37Z |
| publishDate | 2017-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ff843e54053a417491a69848ba66e7b32022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2017-01-01610.7554/eLife.21477Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tailJohanna Ludwigsen0Sabrina Pfennig1Ashish K Singh2Christina Schindler3Nadine Harrer4Ignasi Forné5Martin Zacharias6Felix Mueller-Planitz7https://orcid.org/0000-0001-8273-6473Biomedical Center, Ludwig-Maximilians-Universität München, Munich, GermanyBiomedical Center, Ludwig-Maximilians-Universität München, Munich, GermanyBiomedical Center, Ludwig-Maximilians-Universität München, Munich, GermanyPhysics Department (T38), Technische Universität München, Munich, Germany; Center for Integrated Protein Science Munich, Munich, GermanyBiomedical Center, Ludwig-Maximilians-Universität München, Munich, GermanyBiomedical Center, Ludwig-Maximilians-Universität München, Munich, GermanyPhysics Department (T38), Technische Universität München, Munich, Germany; Center for Integrated Protein Science Munich, Munich, GermanyBiomedical Center, Ludwig-Maximilians-Universität München, Munich, GermanyISWI-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.https://elifesciences.org/articles/21477chromatin remodelingnucleosomeATPaseSnf2 |
| spellingShingle | Johanna Ludwigsen Sabrina Pfennig Ashish K Singh Christina Schindler Nadine Harrer Ignasi Forné Martin Zacharias Felix Mueller-Planitz Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail eLife chromatin remodeling nucleosome ATPase Snf2 |
| title | Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail |
| title_full | Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail |
| title_fullStr | Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail |
| title_full_unstemmed | Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail |
| title_short | Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail |
| title_sort | concerted regulation of iswi by an autoinhibitory domain and the h4 n terminal tail |
| topic | chromatin remodeling nucleosome ATPase Snf2 |
| url | https://elifesciences.org/articles/21477 |
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