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| Status |
Public on May 21, 2021 |
| Title |
H3K4 trimethylation is required for postnatal pancreatic endocrine cell functional maturation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
During pancreas development, endocrine progenitors differentiate into the islet-cell subtypes, which undergo further functional maturation in postnatal islet development. In islet b-cells, genes involved in glucose-stimulated insulin secretion are activated and glucose exposure increases the insulin response as b-cells mature. Here, we investigated the role of H3K4 trimethylation in endocrine cell differentiation and functional maturation by disrupting TrxG complex histone methyltransferase activity in mouse endocrine progenitors. In the embryo, genetic inactivation of TrxG component Dpy30 in NEUROG3+ cells did not affect the number of endocrine progenitors or endocrine cell differentiation. H3K4 trimethylation was progressively lost in postnatal islets and the mice displayed elevated non-fasting and fasting glycemia, as well as impaired glucose tolerance by postnatal day 24. Although postnatal endocrine cell proportions were equivalent to controls, islet RNA-sequencing revealed a downregulation of genes involved in glucose-stimulated insulin secretion and an upregulation of immature b-cell genes. Comparison of histone modification enrichment profiles in NEUROG3+ endocrine progenitors and mature islets suggested that genes downregulated by loss of H3K4 trimethylation more frequently acquire active histone modifications during maturation. Taken together, these findings suggest that H3K4 trimethylation is required for the activation of genes involved in the functional maturation of pancreatic islet endocrine cells.
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| |
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| Overall design |
RNA-sequencing of postnatal day 24 control and Dpy30 knockout islets, including 3 biological replicates
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| |
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| Contributor(s) |
Campbell SA, Bégin J, McDonald CL, Vanderkruk B, Stephan TL, Hoffman BG |
| Citation missing |
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| |
| Submission date |
May 20, 2021 |
| Last update date |
May 23, 2021 |
| Contact name |
Brad Hoffman |
| E-mail(s) |
brad.hoffman@ubc.ca
|
| Organization name |
University of British Columbia
|
| Street address |
Room A4-151 950 W28 Ave
|
| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 2B3 |
| Country |
Canada |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA731470 |
| SRA |
SRP320666 |
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