PT - JOURNAL ARTICLE AU - Beon, Jiyoon AU - Han, Sungwook AU - Park, Seung Eun AU - Hyun, Kwangbeom AU - Lee, Song-Yi AU - Rhee, Hyun-Woo AU - Seo, Jeong Kon AU - Kim, Jaehoon AU - Kim, Seyun AU - Lee, Daeyoup TI - IPMK physically binds to the SWI/SNF complex and modulates BRG1 occupancy AID - 10.1101/2021.09.15.460446 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.09.15.460446 4099 - http://biorxiv.org/content/early/2021/09/15/2021.09.15.460446.short 4100 - http://biorxiv.org/content/early/2021/09/15/2021.09.15.460446.full AB - Inositol polyphosphate multikinase (IPMK), a key enzyme in the inositol polyphosphate (IP) metabolism, is a pleiotropic signaling factor involved in major biological events including transcriptional control. In yeasts, IPMK and its IP products were known to promote the activity of SWI/SNF chromatin remodeling complex, which plays a critical role in gene expression by regulating chromatin accessibility. However, the direct linkage between IPMK and chromatin remodelers remains unclear, raising a question on how IPMK contributes to the transcriptional regulation in mammals. By employing unbiased screenings and in vivo/in vitro immunoprecipitations, here we demonstrated that IPMK physically associates with native mammalian SWI/SNF complexes by directly binding to SMARCB1, BRG1, and SMARCC1. Furthermore, we identified the specific domains required for the IPMK-SMARCB1 binding. Notably, using CUT&RUN and ATAC-seq assays, we discovered that IPMK co-localizes with BRG1 and regulates BRG1 localization as well as BRG1-mediated chromatin accessibility in a genome-wide manner (including promoter-TSS) in mouse embryonic stem cells. Finally, our mRNA-seq analyses revealed that IPMK and SMARCB1 regulate common gene sets, validating a functional link between IPMK and SWI/SNF complex. Together, these findings establish an importance of IPMK in promoter targeting of the SWI/SNF complex, thereby contributing to SWI/SNF-meditated chromatin accessibility and transcription.Competing Interest StatementThe authors have declared no competing interest.