Titre
Identification and analysis of murine pancreatic islet enhancers.
Type
article
Institution
Externe
Périodique
Auteur(s)
Tennant, B.R.
Auteure/Auteur
Robertson, A.G.
Auteure/Auteur
Kramer, M.
Auteure/Auteur
Li, L.
Auteure/Auteur
Zhang, X.
Auteure/Auteur
Beach, M.
Auteure/Auteur
Thiessen, N.
Auteure/Auteur
Chiu, R.
Auteure/Auteur
Mungall, K.
Auteure/Auteur
Whiting, C.J.
Auteure/Auteur
Sabatini, P.V.
Auteure/Auteur
Kim, A.
Auteure/Auteur
Gottardo, R.
Auteure/Auteur
Marra, M.A.
Auteure/Auteur
Lynn, F.C.
Auteure/Auteur
Jones, S.J.
Auteure/Auteur
Hoodless, P.A.
Auteure/Auteur
Hoffman, B.G.
Auteure/Auteur
Liens vers les personnes
ISSN
1432-0428
Statut éditorial
Publié
Date de publication
2013-03
Volume
56
Numéro
3
Première page
542
Dernière page/numéro d’article
552
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
The paucity of information on the epigenetic barriers that are blocking reprogramming protocols, and on what makes a beta cell unique, has hampered efforts to develop novel beta cell sources. Here, we aimed to identify enhancers in pancreatic islets, to understand their developmental ontologies, and to identify enhancers unique to islets to increase our understanding of islet-specific gene expression.
We combined H3K4me1-based nucleosome predictions with pancreatic and duodenal homeobox 1 (PDX1), neurogenic differentiation 1 (NEUROD1), v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MAFA) and forkhead box A2 (FOXA2) occupancy data to identify enhancers in mouse islets.
We identified 22,223 putative enhancer loci in in vivo mouse islets. Our validation experiments suggest that nearly half of these loci are active in regulating islet gene expression, with the remaining regions probably poised for activity. We showed that these loci have at least nine developmental ontologies, and that islet enhancers predominately acquire H3K4me1 during differentiation. We next discriminated 1,799 enhancers unique to islets and showed that these islet-specific enhancers have reduced association with annotated genes, and identified a subset that are instead associated with novel islet-specific long non-coding RNAs (lncRNAs).
Our results indicate that genes with islet-specific expression and function tend to have enhancers devoid of histone methylation marks or, less often, that are bivalent or repressed, in embryonic stem cells and liver. Further, we identify a subset of enhancers unique to islets that are associated with novel islet-specific genes and lncRNAs. We anticipate that these data will facilitate the development of novel sources of functional beta cell mass.
We combined H3K4me1-based nucleosome predictions with pancreatic and duodenal homeobox 1 (PDX1), neurogenic differentiation 1 (NEUROD1), v-Maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MAFA) and forkhead box A2 (FOXA2) occupancy data to identify enhancers in mouse islets.
We identified 22,223 putative enhancer loci in in vivo mouse islets. Our validation experiments suggest that nearly half of these loci are active in regulating islet gene expression, with the remaining regions probably poised for activity. We showed that these loci have at least nine developmental ontologies, and that islet enhancers predominately acquire H3K4me1 during differentiation. We next discriminated 1,799 enhancers unique to islets and showed that these islet-specific enhancers have reduced association with annotated genes, and identified a subset that are instead associated with novel islet-specific long non-coding RNAs (lncRNAs).
Our results indicate that genes with islet-specific expression and function tend to have enhancers devoid of histone methylation marks or, less often, that are bivalent or repressed, in embryonic stem cells and liver. Further, we identify a subset of enhancers unique to islets that are associated with novel islet-specific genes and lncRNAs. We anticipate that these data will facilitate the development of novel sources of functional beta cell mass.
PID Serval
serval:BIB_E969476E1237
PMID
Open Access
Oui
Date de création
2022-02-28T10:45:30.816Z
Date de création dans IRIS
2025-05-21T06:13:01Z