文献求助：Genes & Development

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http://genesdev.cshlp.org/conten ... stract.html?papetoc
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6 R9 B5 l+ |7 b/ WRing1b bookmarks genes in pancreatic embryonic progenitors for repression in adult β cells
& F  t0 ?8 p, q  j; sJoris van Arensbergen1,2,6, Javier García-Hurtado1,2, Miguel Angel Maestro1,2, Miguel Correa-Tapia1,2, Guy A. Rutter3, Miguel Vidal4 and Jorge Ferrer1,2,3,5; q6 G7 Y+ F: k( O! x* v
+ Author Affiliations
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$ U' p( U! A& B5 E) z1Genomic Programming of Beta Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain;8 @/ ]: l# _7 o' g
2Centros de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas, 08036 Barcelona, Spain;
3 Q, `- ?) _" `( D1 n0 m8 P/ q1 F9 R7 f3Department of Medicine, Imperial College, London W12 0NN, United Kingdom;
6 ^! I6 ]9 S5 l" |$ y( D9 A4 l4Cellular and Molecular Biology, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), 28040 Madrid, Spain;
( I2 S# m. u1 ^' `5Department of Endocrinology, Hospital Clínic de Barcelona, 08036 Barcelona, Spain
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↵6 Present address: Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands
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Abstract2 Q7 u2 @1 ^" h
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Polycomb-mediated gene repression is essential for embryonic development, yet its precise role in lineage-specific programming is poorly understood. Here we inactivated Ring1b, encoding a polycomb-repressive complex 1 subunit, in pancreatic multipotent progenitors (Ring1bprogKO). This caused transcriptional derepression of a subset of direct Ring1b target genes in differentiated pancreatic islet cells. Unexpectedly, Ring1b inactivation in differentiated islet β cells (Ring1bβKO) did not cause derepression, even after multiple rounds of cell division, suggesting a role for Ring1b in the establishment but not the maintenance of repression. Consistent with this notion, derepression in Ring1bprogKO islets occurred preferentially in genes that were targeted de novo by Ring1b during pancreas development. The results support a model in which Ring1b bookmarks its target genes during embryonic development, and these genes are maintained in a repressed state through Ring1b-independent mechanisms in terminally differentiated cells. This work provides novel insights into how epigenetic mechanisms contribute to shaping the transcriptional identity of differentiated lineages.

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