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The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming.
- Source :
-
Nature communications [Nat Commun] 2023 Aug 04; Vol. 14 (1), pp. 4682. Date of Electronic Publication: 2023 Aug 04. - Publication Year :
- 2023
-
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 <subscript>M</subscript> ). 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.<br /> (© 2023. Springer Nature Limited.)
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 37542049
- Full Text :
- https://doi.org/10.1038/s41467-023-40386-8