Inositol polyphosphate multikinase physically binds to the SWI/SNF complex and modulates BRG1 occupancy in mouse
Jiyoon Beon1, Sungwook Han1, Hyeokjun Yang1
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.
Elife
|May 13, 2022
Summary
Inositol polyphosphate multikinase (IPMK) interacts with the SWI/SNF complex in mammals, regulating chromatin accessibility and gene transcription. This discovery clarifies IPMK
Area of Science:
- Molecular Biology
- Epigenetics
- Cell Biology
Background:
- Inositol polyphosphate multikinase (IPMK) is crucial for inositol polyphosphate metabolism and transcriptional control.
- In yeast, IPMK and its products enhance SWI/SNF chromatin remodeling complex activity, but its mammalian role is unclear.
Purpose of the Study:
- To elucidate the direct interaction and functional role of mammalian IPMK in transcriptional regulation via the SWI/SNF complex.
Main Methods:
- Unbiased screening, immunoprecipitation (in vivo/in vitro), domain identification, CUT&RUN, ATAC-seq.
Main Results:
- Mammalian IPMK directly binds to SWI/SNF components SMARCB1, BRG1, and SMARCC1.
- IPMK regulates genome-wide chromatin accessibility and BRG1 localization in mouse embryonic stem cells.
- Specific domains mediate IPMK-SMARCB1 binding.
Conclusions:
- IPMK physically interacts with and regulates the SWI/SNF complex in mammals.
- IPMK controls SWI/SNF targeting, chromatin accessibility, transcription, and differentiation in mouse embryonic stem cells.
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