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Series GSE37774 Query DataSets for GSE37774
Status Public on Jun 01, 2012
Title Genome-wide characterization of menin-dependent H3K4me3 reveals a specific role for menin in the regulation of genes implicated in MEN1-like tumors (ChIP-Seq)
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Inactivating mutations in the MEN1 gene predisposing to the multiple endocrine neoplasia type 1 (MEN1) syndrome can also cause sporadic pancreatic endocrine tumors. MEN1 encodes menin, a subunit of MLL1/MLL2-containing histone methyltransferase complexes that trimethylate histone H3 at lysine 4 (H3K4me3). The importance of menin-dependent H3K4me3 in normal and transformed pancreatic endocrine cells is unclear. To study the role of menin-dependent H3K4me3, we performed in vitro differentiation of wild-type as well as menin-null mouse embryonic stem cells (mESCs) into pancreatic islet-like endocrine cells (PILECs). Gene expression analysis and genome-wide H3K4me3 ChIP-Seq profiling in wild-type and menin-null mESCs and PILECs revealed menin-dependent H3K4me3 at the imprinted Dlk1-Meg3 locus in mESCs, and all four Hox loci in differentiated PILECs. Specific and significant loss of H3K4me3 and gene expression was observed for genes within the imprinted Dlk1-Meg3 locus in menin-null mESCs and the Hox loci in menin-null PILECs. Given that the reduced expression of genes within the DLK1-MEG3 locus and the HOX loci is associated with MEN1-like sporadic tumors, our data suggests a possible role for menin-dependent H3K4me3 at these genes in the initiation and progression of sporadic pancreatic endocrine tumors. Furthermore, our investigation also demonstrates that menin-null mESCs can be differentiated in vitro into islet-like endocrine cells, underscoring the utility of menin-null mESC-derived specialized cell types for genome-wide high-throughput studies.
 
Overall design Genome-wide mapping of H3K4me3 and microarray gene expression profiling in TC-1 wild-type (WT) mESCs, menin-null (Men1-ko) mESCs (3.2N), pancreatic islet-like endocrine cells (PILECs) derived from WT mESCs, and PILECs derived from Men1-ko mESCs.
 
Contributor(s) Agarwal S, Jothi R
Citation(s) 22666422
Submission date May 04, 2012
Last update date May 15, 2019
Contact name Raja Jothi
E-mail(s) jothi@mail.nih.gov
Organization name National Institutes of Health
Department National Institute of Environmental Health Sciences
Lab Systems Biology
Street address 111 TW Alexander Drive; A314
City RTP
State/province NC
ZIP/Postal code 27709
Country USA
 
Platforms (1)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
Samples (8)
GSM928125 WT ES cells, Control Input
GSM928126 Men1-KO ES cells, Control Input
GSM928127 WT ES cells, H3K4me3 ChIP
This SubSeries is part of SuperSeries:
GSE37776 Genome-wide characterization of menin-dependent H3K4me3 reveals a specific role for menin in the regulation of genes implicated in MEN1-like tumors
Relations
SRA SRP012696
BioProject PRJNA163661

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Supplementary file Size Download File type/resource
GSE37774_RAW.tar 852.3 Mb (http)(custom) TAR (of BED)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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