ArrayExpress Uploader0mouseES cellWild-typeES cellWild-typeES cellMen1-KOES cellMen1-KOES cells were differentiated into pancreatic islet-like endocrine cells (PILECs)Wild-typeES cells were differentiated into pancreatic islet-like endocrine cells (PILECs)Wild-typeES cells were differentiated into pancreatic islet-like endocrine cells (PILECs)Men1-KOES cells were differentiated into pancreatic islet-like endocrine cells (PILECs)Men1-KO6872arrayexpress_sid6Inactivating mutations in the MEN1 gene predisposing to the multiple endocrine neoplasia type 1 (MEN1) syndrome can also cause sporadic...E-GEOD-37775/profile/8773/arrayexpressuploader28cellgenomehistonehistone h3lysinemultiple endocrine neoplasiamultiple endocrine neoplasia type 1pancreatic isletsyndromeDec.12, 2014Falsegenome-wide-characterization-of-menin-dependent-h3E-GEOD-37775_A-AFFY-45Genome-wide characterization of menin-dependent H3K4me3 reveals a specific role for menin in the regulation of genes implicated in MEN1-like tumors (mRNA)Nov.12, 2014Inactivating 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. 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.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-37775http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-37775/samples/