Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription


ABSTRACT: Insulin (INS) synthesis and secretion from pancreatic M-NM-2 cells are tightly regulated; their deregulation causes diabetes. Here we map INS-associated loci in human pancreatic islets by 4C and 3C techniques and show that the INS gene physically interacts with the SYT8 gene, located over 300 kb away. This interaction is elevated by glucose and accompanied by increases in SYT8 expression. Inactivation of the INS promoter by promoter-targeting siRNA reduces SYT8 gene expression. SYT8-INS interaction and SYT8 transcription are attenuated by CTCF depletion. Furthermore, SYT8 knockdown decreases insulin secretion in islets. These results reveal a non-redundant role for SYT8 in insulin secretion and indicate that the INS promoter acts from a distance to stimulate SYT8 transcription. This suggests a function for the INS promoter in coordinating insulin transcription and secretion through long-range regulation of SYT8 expression in human islets. Circular Chromosome Conformation Capture (4C)-Seq experiments to profile interactions of INS promoter in human pancreatic islets isolated from two donors: donor 1 and donor 2.

ORGANISM(S): Homo sapiens

SUBMITTER: Iouri Chepelev 

PROVIDER: E-GEOD-25862 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

Mapping of INS promoter interactions reveals its role in long-range regulation of SYT8 transcription.

Xu Zhixiong Z   Wei Gang G   Chepelev Iouri I   Zhao Keji K   Felsenfeld Gary G  

Nature structural & molecular biology 20110220 3


Insulin (INS) synthesis and secretion from pancreatic β-cells are tightly regulated; their deregulation causes diabetes. Here we map INS-associated loci in human pancreatic islets by 4C and 3C techniques and show that the INS gene physically interacts with the SYT8 gene, located over 300 kb away. This interaction is elevated by glucose and accompanied by increases in SYT8 expression. Inactivation of the INS promoter by promoter-targeting siRNA reduces SYT8 gene expression. SYT8-INS interaction a  ...[more]

Similar Datasets

2016-07-03 | E-GEOD-67991 | biostudies-arrayexpress
2012-08-30 | E-GEOD-16048 | biostudies-arrayexpress
2023-11-05 | PXD038554 | Pride
2011-02-22 | GSE25862 | GEO
2023-11-16 | PXD041616 | Pride
2012-09-09 | E-GEOD-40709 | biostudies-arrayexpress
2013-12-01 | E-GEOD-52314 | biostudies-arrayexpress
2008-10-20 | E-GEOD-8873 | biostudies-arrayexpress
2010-05-18 | E-GEOD-13153 | biostudies-arrayexpress
2014-07-11 | E-GEOD-59285 | biostudies-arrayexpress