1. The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming.
- Author
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Saha D, Hailu S, Hada A, Lee J, Luo J, Ranish JA, Lin YC, Feola K, Persinger J, Jain A, Liu B, Lu Y, Sen P, and Bartholomew B
- Subjects
- Animals, Mice, Cell Lineage genetics, Chromatin, Nucleosomes genetics, DNA metabolism, Adenosine Triphosphate metabolism, Transcription Factors metabolism, Saccharomyces cerevisiae genetics, Saccharomyces cerevisiae metabolism
- Abstract
The SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome, controlling pluripotency and differentiation. Towards the C-terminus of the catalytic subunit of SWI/SNF is a motif called the AT-hook that is evolutionary conserved. The AT-hook is present in many chromatin modifiers and generally thought to help anchor them to DNA. We observe however that the AT-hook regulates the intrinsic DNA-stimulated ATPase activity aside from promoting SWI/SNF recruitment to DNA or nucleosomes by increasing the reaction velocity a factor of 13 with no accompanying change in substrate affinity (K
M ). The changes in ATP hydrolysis causes an equivalent change in nucleosome movement, confirming they are tightly coupled. The catalytic subunit's AT-hook is required in vivo for SWI/SNF remodeling activity in yeast and mouse embryonic stem cells. The AT-hook in SWI/SNF is required for transcription regulation and activation of stage-specific enhancers critical in cell lineage priming. Similarly, growth assays suggest the AT-hook is required in yeast SWI/SNF for activation of genes involved in amino acid biosynthesis and metabolizing ethanol. Our findings highlight the importance of studying SWI/SNF attenuation versus eliminating the catalytic subunit or completely shutting down its enzymatic activity., (© 2023. Springer Nature Limited.)- Published
- 2023
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