Biophysical Society Thematic Meeting| Santa Cruz 2018

Genome Biophysics: Integrating Genomics and Biophysics to Understand Structural and Functional Aspects of Genomes

Poster Abstracts

7-POS

Board 7

Regulation of Rapid Nucleosome Sliding by Substrate Cues and Accessory Subunits in the Yeast INO80 Chromatin Remodeling Complex Stephanie L. Johnson 1 , Coral Y. Zhou 1 , Laura J. Lee 1 , Matthew J. Johnson 2 , Adam D. Longhurst 1 , Geeta J. Narlikar 1 . 1 University of California, San Francisco, San Francisco, CA, USA, 2 Google Brain, San Francisco, CA, USA. Chromatin remodeling complexes are molecular motors that catalyze diverse structural rearrangements to nucleosomes. As such, they are involved in many fundamental gene regulatory processes through their manipulation of genome structure. The INO80 family is the most recently discovered of the four main remodeler families. Despite INO80’s roles in essential processes such as DNA damage repair and the establishment of promoter architectures, the biophysical mechanisms of INO80-family remodelers remain some of the most elusive. Here we describe a mechanistic dissection of the large, multi-subunit yeast INO80 complex, using a combined ensemble biochemistry/single-molecule biophysics approach. We show that (i) INO80 exhibits a switch-like response to flanking DNA length, which is “tuned” by an auto-inhibitory module in the complex; (ii) once sliding is initiated, INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess flanking DNA length; and (iii) INO80 can change the direction of nucleosome sliding without dissociation. We present a model for INO80 as a highly processive remodeling motor that is tightly regulated by both substrate cues and non-catalytic subunits of the complex, which may specialize INO80 for its particular in vivo roles.

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