التفاصيل البيبلوغرافية
| العنوان: |
The p300 and CBP Transcriptional Coactivators Are Required for β-Cell and α-Cell Proliferation. |
| المؤلفون: |
Chi Kin Wong, Wade-Vallance, Adam K., Luciani, Dan S., Brindle, Paul K., Lynn, Francis C., Gibson, William T. |
| المصدر: |
Diabetes; Mar2018, Vol. 67 Issue 3, p412-422, 11p |
| مصطلحات موضوعية: |
BLOOD sugar analysis, PROTEIN metabolism, ANIMAL experimentation, ANIMAL populations, CELL physiology, COMPARATIVE studies, GENES, GENETIC techniques, INSULIN, ISLANDS of Langerhans, LYSINE, RESEARCH methodology, MEDICAL cooperation, METABOLISM, MICE, PROTEINS, RESEARCH, RESEARCH funding, STEM cells, TRANSFERASES, EVALUATION research, GLUCOSE intolerance, CELL size |
| مستخلص: |
p300 (EP300) and CBP (CREBBP) are transcriptional coactivators with histone acetyltransferase activity. Various β-cell transcription factors can recruit p300/CBP, and thus the coactivators could be important for β-cell function and health in vivo. We hypothesized that p300/CBP contribute to the development and proper function of pancreatic islets. To test this, we bred and studied mice lacking p300/CBP in their islets. Mice lacking either p300 or CBP in islets developed glucose intolerance attributable to impaired insulin secretion, together with reduced α- and β-cell area and islet insulin content. These phenotypes were exacerbated in mice with only a single copy of p300 or CBP expressed in islets. Removing p300 in pancreatic endocrine progenitors impaired proliferation of neonatal α- and β-cells. Mice lacking all four copies of p300/CBP in pancreatic endocrine progenitors failed to establish α- and β-cell mass postnatally. Transcriptomic analyses revealed significant overlaps between p300/CBP-downregulated genes and genes downregulated in Hnf1α-null islets and Nkx2.2-null islets, among others. Furthermore, p300/CBP are important for the acetylation of H3K27 at loci downregulated in Hnf1α-null islets. We conclude that p300 and CBP are limiting cofactors for islet development, and hence for postnatal glucose homeostasis, with some functional redundancy. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
