Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks
(2017) In Cell Metabolism 25(2). p.400-411- Abstract
Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D... (More)
Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.
(Less)
- author
- organization
- publishing date
- 2017-02-07
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- chromatin, CRISPR interference, diabetes, lncRNAs, long noncoding RNAs, pancreatic islets, PDX1, PLUTO, transcriptional networks, type 2 diabetes
- in
- Cell Metabolism
- volume
- 25
- issue
- 2
- pages
- 12 pages
- publisher
- Cell Press
- external identifiers
-
- pmid:28041957
- wos:000396354400020
- scopus:85009909783
- ISSN
- 1550-4131
- DOI
- 10.1016/j.cmet.2016.11.016
- language
- English
- LU publication?
- yes
- id
- 28c0f789-ce8e-46e1-805b-d7d4a577fcfa
- date added to LUP
- 2017-04-19 11:29:06
- date last changed
- 2025-02-03 14:17:27
@article{28c0f789-ce8e-46e1-805b-d7d4a577fcfa, abstract = {{<p>Recent studies have uncovered thousands of long non-coding RNAs (lncRNAs) in human pancreatic β cells. β cell lncRNAs are often cell type specific and exhibit dynamic regulation during differentiation or upon changing glucose concentrations. Although these features hint at a role of lncRNAs in β cell gene regulation and diabetes, the function of β cell lncRNAs remains largely unknown. In this study, we investigated the function of β cell-specific lncRNAs and transcription factors using transcript knockdowns and co-expression network analysis. This revealed lncRNAs that function in concert with transcription factors to regulate β cell-specific transcriptional networks. We further demonstrate that the lncRNA PLUTO affects local 3D chromatin structure and transcription of PDX1, encoding a key β cell transcription factor, and that both PLUTO and PDX1 are downregulated in islets from donors with type 2 diabetes or impaired glucose tolerance. These results implicate lncRNAs in the regulation of β cell-specific transcription factor networks.</p>}}, author = {{Akerman, Ildem and Tu, Zhidong and Beucher, Anthony and Rolando, Delphine M Y and Sauty-Colace, Claire and Benazra, Marion and Nakic, Nikolina and Yang, Jialiang and Wang, Huan L. and Pasquali, Lorenzo and Moran, Ignasi and Garcia-Hurtado, Javier and Castro, Natalia and Gonzalez-Franco, Roser and Stewart, Andrew F. and Bonner, Caroline and Piemonti, Lorenzo and Berney, Thierry and Groop, Leif and Kerr-Conte, Julie and Pattou, Francois and Argmann, Carmen and Schadt, Eric and Ravassard, Philippe and Ferrer, Jorge}}, issn = {{1550-4131}}, keywords = {{chromatin; CRISPR interference; diabetes; lncRNAs; long noncoding RNAs; pancreatic islets; PDX1; PLUTO; transcriptional networks; type 2 diabetes}}, language = {{eng}}, month = {{02}}, number = {{2}}, pages = {{400--411}}, publisher = {{Cell Press}}, series = {{Cell Metabolism}}, title = {{Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks}}, url = {{http://dx.doi.org/10.1016/j.cmet.2016.11.016}}, doi = {{10.1016/j.cmet.2016.11.016}}, volume = {{25}}, year = {{2017}}, }