Human pancreatic β cell lncRNAs control cell-specific regulatory networks

Ildem Akerman; Zhidong Tu; Anthony Beucher; Delphine M. Y. Rolando; Claire Sauty-Colace; Marion Benazra; Nikolina Nakic; Jialiang Yang; Huan Wang; Lorenzo Pasquali; Ignasi Moran; Javier Garcia-Hurtado; Natalia Castro; Roser Gonzalez-Franco; Andrew F. Stewart; Caroline Bonner; Lorenzo Piemonti; Thierry Berney; Leif Groop; Julie Kerr-Conte; Francois Pattou; Carmen Argmann; Eric Schadt; Philippe Ravassard; Jorge Ferrer

doi:10.1016/j.cmet.2016.11.016

Human pancreatic β cell lncRNAs control cell-specific regulatory networks

Ildem Akerman, Zhidong Tu, Anthony Beucher, Delphine M. Y. Rolando, Claire Sauty-Colace, Marion Benazra, Nikolina Nakic, Jialiang Yang, Huan Wang, Lorenzo Pasquali, Ignasi Moran, Javier Garcia-Hurtado, Natalia Castro, Roser Gonzalez-Franco, Andrew F. Stewart, Caroline Bonner, Lorenzo Piemonti, Thierry Berney, Leif Groop, Julie Kerr-ConteFrancois Pattou, Carmen Argmann, Eric Schadt, Philippe Ravassard, Jorge Ferrer

Metabolism and Systems Research

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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 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.

Original language	English
Pages (from-to)	400-411
Number of pages	12
Journal	Cell Metabolism
Volume	25
Issue number	2
Early online date	29 Dec 2016
DOIs	https://doi.org/10.1016/j.cmet.2016.11.016
Publication status	Published - 7 Feb 2017

Keywords

Chromatin
Diabetes Mellitus, Type 2
Gene Expression Regulation
Gene Knockdown Techniques
Gene Regulatory Networks
Homeodomain Proteins
Humans
Insulin
Insulin-Secreting Cells
Multigene Family
Phenotype
RNA, Long Noncoding
RNA, Messenger
Trans-Activators
Transcription Factors
Transcription, Genetic
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cmet.2016.11.016Licence: Creative Commons: Attribution (CC BY)

Akerman_et_al_Human_pancreatic_β_cell_Cell_Metabolism_2016
Published in Cell Metabolism on 29/12/2016 DOI: 10.1016/j.cmet.2016.11.016
Final published version, 3.45 MBLicence: Creative Commons: Attribution (CC BY)

Cite this

Akerman, I., Tu, Z., Beucher, A., Rolando, D. M. Y., Sauty-Colace, C., Benazra, M., Nakic, N., Yang, J., Wang, H., Pasquali, L., Moran, I., Garcia-Hurtado, J., Castro, N., Gonzalez-Franco, R., Stewart, A. F., Bonner, C., Piemonti, L., Berney, T., Groop, L., ... Ferrer, J. (2017). Human pancreatic β cell lncRNAs control cell-specific regulatory networks. Cell Metabolism, 25(2), 400-411. Advance online publication. https://doi.org/10.1016/j.cmet.2016.11.016

@article{388c6840d52a4c5e95a2118a965ad134,

title = "Human pancreatic β cell lncRNAs control cell-specific regulatory networks",

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 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.",

keywords = "Chromatin, Diabetes Mellitus, Type 2, Gene Expression Regulation, Gene Knockdown Techniques, Gene Regulatory Networks, Homeodomain Proteins, Humans, Insulin, Insulin-Secreting Cells, Multigene Family, Phenotype, RNA, Long Noncoding, RNA, Messenger, Trans-Activators, Transcription Factors, Transcription, Genetic, Journal Article",

author = "Ildem Akerman and Zhidong Tu and Anthony Beucher and Rolando, {Delphine M. Y.} and Claire Sauty-Colace and Marion Benazra and Nikolina Nakic and Jialiang Yang and Huan Wang and Lorenzo Pasquali and Ignasi Moran and Javier Garcia-Hurtado and Natalia Castro and Roser Gonzalez-Franco and Stewart, {Andrew F.} and Caroline Bonner and Lorenzo Piemonti and Thierry Berney and Leif Groop and Julie Kerr-Conte and Francois Pattou and Carmen Argmann and Eric Schadt and Philippe Ravassard and Jorge Ferrer",

year = "2017",

month = feb,

day = "7",

doi = "10.1016/j.cmet.2016.11.016",

language = "English",

volume = "25",

pages = "400--411",

journal = "Cell Metabolism",

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Akerman, I, Tu, Z, Beucher, A, Rolando, DMY, Sauty-Colace, C, Benazra, M, Nakic, N, Yang, J, Wang, H, Pasquali, L, Moran, I, Garcia-Hurtado, J, Castro, N, Gonzalez-Franco, R, Stewart, AF, Bonner, C, Piemonti, L, Berney, T, Groop, L, Kerr-Conte, J, Pattou, F, Argmann, C, Schadt, E, Ravassard, P & Ferrer, J 2017, 'Human pancreatic β cell lncRNAs control cell-specific regulatory networks', Cell Metabolism, vol. 25, no. 2, pp. 400-411. https://doi.org/10.1016/j.cmet.2016.11.016

TY - JOUR

T1 - Human pancreatic β cell lncRNAs control cell-specific regulatory networks

AU - Akerman, Ildem

AU - Tu, Zhidong

AU - Beucher, Anthony

AU - Rolando, Delphine M. Y.

AU - Sauty-Colace, Claire

AU - Benazra, Marion

AU - Nakic, Nikolina

AU - Yang, Jialiang

AU - Wang, Huan

AU - Pasquali, Lorenzo

AU - Moran, Ignasi

AU - Garcia-Hurtado, Javier

AU - Castro, Natalia

AU - Gonzalez-Franco, Roser

AU - Stewart, Andrew F.

AU - Bonner, Caroline

AU - Piemonti, Lorenzo

AU - Berney, Thierry

AU - Groop, Leif

AU - Kerr-Conte, Julie

AU - Pattou, Francois

AU - Argmann, Carmen

AU - Schadt, Eric

AU - Ravassard, Philippe

AU - Ferrer, Jorge

PY - 2017/2/7

Y1 - 2017/2/7

N2 - 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.

AB - 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.

KW - Chromatin

KW - Diabetes Mellitus, Type 2

KW - Gene Expression Regulation

KW - Gene Knockdown Techniques

KW - Gene Regulatory Networks

KW - Homeodomain Proteins

KW - Humans

KW - Insulin

KW - Insulin-Secreting Cells

KW - Multigene Family

KW - Phenotype

KW - RNA, Long Noncoding

KW - RNA, Messenger

KW - Trans-Activators

KW - Transcription Factors

KW - Transcription, Genetic

KW - Journal Article

U2 - 10.1016/j.cmet.2016.11.016

DO - 10.1016/j.cmet.2016.11.016

M3 - Article

C2 - 28041957

SN - 1550-4131

VL - 25

SP - 400

EP - 411

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

Human pancreatic β cell lncRNAs control cell-specific regulatory networks

Abstract

Keywords

UN SDGs

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