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Series GSE134901 Query DataSets for GSE134901
Status Public on Feb 24, 2023
Title Nutrient regulation of the islet epigenome controls adaptive insulin secretion
Organisms Homo sapiens; Mus; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Adaptation of the islet β-cell insulin secretory response to changing insulin demand is critical for blood glucose homeostasis, yet the mechanisms underlying this adaptation are unknown. Here, we show that nutrient cues adapt insulin secretion by modulating chromatin state and transcription of genes regulating β-cell nutrient sensing and metabolism. Feeding stimulates histone acetylation at sites occupied by the chromatin-modifying enzyme Lsd1 in islets. We demonstrate that β-cell-specific deletion of Lsd1 leads to insulin hypersecretion, aberrant expression of nutrient response genes, and histone hyperacetylation, features we also observed in the db/db model of chronically increased insulin demand. Moreover, genetic variants associated with fasting glucose levels and type 2 diabetes risk are enriched at LSD1-bound sites in human islets, suggesting interindividual variation in β-cell functional adaptation in humans. These findings reveal nutrient state-dependent modulation of the islet epigenome and identify Lsd1 as a regulator of feeding-stimulated chromatin modification and adaptive insulin secretion.
Overall design Human or mouse pancreatic islets were assessed for genomewide enrichment of H3K27ac under different conditions or for binding by the histone demethylase Lsd1 using ChIP-seq. mRNA-seq was used to assess transcriptional changes in islets under different nutrient states or following inactivation of the histone demethylase Lsd1.
Contributor(s) Wortham M
Citation(s) 36821378
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 DK068471 Epigenetic determinants of beta cell development and function THE REGENTS OF THE UNIV. OF CALIF., UNIV. OF CALIF., SAN DIEGO Maike Sander
S10 OD026929 Illumina NovaSeq 6000 Sequencing System THE REGENTS OF THE UNIV. OF CALIF., UNIV. OF CALIF., SAN DIEGO Kristen Lynn Jepsen
Submission date Jul 25, 2019
Last update date May 12, 2023
Contact name Matthew Wortham
Phone 8582460588
Organization name University of California, San Diego
Lab Maike Sander
Street address 2880 Torrey Pines Scenic Drive, Sanford Consortium for Regenerative Medicine, Room 3102
City La Jolla
State/province CA
ZIP/Postal code 92037
Country USA
Platforms (4)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (131)
GSM3978562 Hs_islets_LSD1_ChIPseq_A
GSM3978563 Hs_islets_input_A
GSM3978564 Hs_islets_LSD1_ChIPseq_B
BioProject PRJNA556715
SRA SRP216428

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE134901_10pmFastMe1Merge.ucsc.bedGraph.gz 28.2 Mb (ftp)(http) BEDGRAPH
GSE134901_10pmFedFast.diff.gz 827.6 Kb (ftp)(http) DIFF
GSE134901_10pmFedMe1Merge.ucsc.bedGraph.gz 27.2 Mb (ftp)(http) BEDGRAPH
GSE134901_10pmfast27ac.ucsc.bedGraph.gz 48.0 Mb (ftp)(http) BEDGRAPH
GSE134901_10pmfastinput.ucsc.bedGraph.gz 53.3 Mb (ftp)(http) BEDGRAPH
GSE134901_10pmfed27ac.ucsc.bedGraph.gz 61.9 Mb (ftp)(http) BEDGRAPH
GSE134901_10pmfedinput.ucsc.bedGraph.gz 57.9 Mb (ftp)(http) BEDGRAPH
GSE134901_3_Input_mouse_s2.fastq.gz.dir.ucsc.bedGraph.gz 52.9 Mb (ftp)(http) BEDGRAPH
GSE134901_7_LSD1_Chow_s_2_sequence.fastq.gz.dir.ucsc.bedGraph.gz 50.6 Mb (ftp)(http) BEDGRAPH
GSE134901_CombinedFastInputforLsd1.ucsc.bedGraph.gz 508.2 Mb (ftp)(http) BEDGRAPH
GSE134901_CombinedFastLsd1.ucsc.bedGraph.gz 30.5 Mb (ftp)(http) BEDGRAPH
GSE134901_CombinedFedInputforLsd1.ucsc.bedGraph.gz 581.1 Mb (ftp)(http) BEDGRAPH
GSE134901_CombinedFedLsd1.ucsc.bedGraph.gz 43.1 Mb (ftp)(http) BEDGRAPH
GSE134901_Ctrld21NEWme1.ucsc.bedGraph.gz 25.3 Mb (ftp)(http) BEDGRAPH
GSE134901_CtrlforLsdKI_H3K27ac1e8.ucsc.bedGraph.gz 43.7 Mb (ftp)(http) BEDGRAPH
GSE134901_FastAcABC250_10e7.ucsc.bedGraph.gz 109.7 Mb (ftp)(http) BEDGRAPH
GSE134901_FedAcABC250_10e7.ucsc.bedGraph.gz 105.2 Mb (ftp)(http) BEDGRAPH
GSE134901_HuIsletInputforLsdOld+B.ucsc.bedGraph.gz 42.8 Mb (ftp)(http) BEDGRAPH
GSE134901_HuIsletLsd1Old+B.ucsc.bedGraph.gz 36.6 Mb (ftp)(http) BEDGRAPH
GSE134901_KO_NEW_me1.ucsc.bedGraph.gz 25.9 Mb (ftp)(http) BEDGRAPH
GSE134901_Lsd1KI_Wk3_gene_exp.txt.gz 812.0 Kb (ftp)(http) TXT
GSE134901_Lsd1KO_Wk1FastFed_gene_exp.txt.gz 1.7 Mb (ftp)(http) TXT
GSE134901_Lsd1KO_Wk1_gene_exp.diff.gz 822.2 Kb (ftp)(http) DIFF
GSE134901_Lsd1KO_Wk3_gene_exp.diff.gz 839.7 Kb (ftp)(http) DIFF
GSE134901_LsdKIWk3_H3K27ac_H3K27ac1e8.ucsc.bedGraph.gz 40.5 Mb (ftp)(http) BEDGRAPH
GSE134901_Min6_SrfAB.ucsc.bedGraph.gz 174.0 Mb (ftp)(http) BEDGRAPH
GSE134901_MsInputforLsdnew.ucsc.bedGraph.gz 15.7 Mb (ftp)(http) BEDGRAPH
GSE134901_TCP_gene_exp.diff.gz 2.1 Mb (ftp)(http) DIFF
GSE134901_ctrl_27ac.ucsc.bedGraph.gz 31.4 Mb (ftp)(http) BEDGRAPH
GSE134901_ctrl_d7input.ucsc.bedGraph.gz 31.6 Mb (ftp)(http) BEDGRAPH
GSE134901_ctrl_input.ucsc.bedGraph.gz 30.4 Mb (ftp)(http) BEDGRAPH
GSE134901_ctrl_me1_d7.ucsc.bedGraph.gz 25.9 Mb (ftp)(http) BEDGRAPH
GSE134901_d7_KO_27ac.ucsc.bedGraph.gz 26.5 Mb (ftp)(http) BEDGRAPH
GSE134901_d7_ctrl_27ac.ucsc.bedGraph.gz 28.1 Mb (ftp)(http) BEDGRAPH
GSE134901_db_gene_exp.diff.gz 782.4 Kb (ftp)(http) DIFF
GSE134901_dbdb_H3K27ac.ucsc.bedGraph.gz 30.5 Mb (ftp)(http) BEDGRAPH
GSE134901_dbdb_H3K4me1.ucsc.bedGraph.gz 29.0 Mb (ftp)(http) BEDGRAPH
GSE134901_dbdb_input.ucsc.bedGraph.gz 33.4 Mb (ftp)(http) BEDGRAPH
GSE134901_dbhet_H3K27ac.ucsc.bedGraph.gz 29.0 Mb (ftp)(http) BEDGRAPH
GSE134901_dbhet_H3K4me1.ucsc.bedGraph.gz 28.7 Mb (ftp)(http) BEDGRAPH
GSE134901_dhet_input.ucsc.bedGraph.gz 32.6 Mb (ftp)(http) BEDGRAPH
GSE134901_koD7_me1.ucsc.bedGraph.gz 25.6 Mb (ftp)(http) BEDGRAPH
GSE134901_ko_27ac.ucsc.bedGraph.gz 24.2 Mb (ftp)(http) BEDGRAPH
GSE134901_ko_d7input.ucsc.bedGraph.gz 29.8 Mb (ftp)(http) BEDGRAPH
GSE134901_ko_input.ucsc.bedGraph.gz 28.8 Mb (ftp)(http) BEDGRAPH
GSE134901_mm_Min6_Untreated_Input_ChIPseq_EF.ucsc.bedGraph.gz 231.1 Mb (ftp)(http) BEDGRAPH
GSE134901_msIsletLsd1new.ucsc.bedGraph.gz 29.1 Mb (ftp)(http) BEDGRAPH
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