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Series GSE128945 Query DataSets for GSE128945
Status Public on Jun 01, 2019
Title The Pdx1 bound Swi/Snf chromatin remodeling complex regulates pancreatic progenitor cell proliferation and mature islet β cell function
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Transcription factors positively and/or negatively impact gene expression by recruiting coregulatory factors, which interact through protein-protein binding. Here we demonstrate that mouse pancreas size and islet β cell function are controlled by the ATP-dependent Swi/Snf chromatin-remodeling coregulatory complex that physically associates with Pdx1, a diabetes-linked transcription factor essential to pancreatic morphogenesis and adult islet-cell function and maintenance. Early embryonic deletion of just the Swi/Snf Brg1 ATPase subunit reduced multipotent pancreatic progenitor cell proliferation and resulted in pancreas hypoplasia. In contrast, removal of both Swi/Snf ATPase subunits, Brg1 and Brm, were required to compromise adult islet β cell activity, which included whole animal glucose intolerance, hyperglycemia and impaired insulin secretion. Notably, lineage-tracing analysis revealed that these Swi/Snf deficient β cells lost the ability to produce insulin and other key metabolic genes, yet the expression levels of many essential islet-enriched transcription factors were unaffected. Swi/Snf was necessary for Pdx1 binding to the insulin enhancer, demonstrating the importance of this association in mediating chromatin accessibility. These results illustrate how fundamental the Pdx1:Swi/Snf coregulator complex is in the pancreas and we discuss how disrupting their association could influence Type 1 and Type 2 diabetes susceptibility.
Overall design Comparison of TdTomato flow-sorted Swi/Snf-deficient islet β cells to those from TdTomato flow-sorted control islet β cells
Contributor(s) Spaeth JM, Stein R
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Submission date Mar 27, 2019
Last update date Jun 03, 2019
Contact name Jason Spaeth
Phone 3172748986
Organization name Indiana University
Department Pediatrics
Lab MS2021
Street address 635 Barnhill Dr.
City Indianapolis
State/province IN
ZIP/Postal code 46202
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM3688762 Control_sorted_1
GSM3688763 Control_sorted_2
GSM3688764 Control_sorted_3
BioProject PRJNA529443
SRA SRP189630

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GSE128945_GEO_Processed_Data_File_Matrix.xlsx.gz 1.9 Mb (ftp)(http) XLSX
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