Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from pancreatic islets from Men1flf RIP-Cre mice, Rbp2flf RIP-Cre mice, Men1flf Rbp2flf RIP-Cre mice and matched control.

ABSTRACT: The menin tumor suppressor protein (Men1) is deficient in many endocrine tumors and forms an active complex with MLL family histone methyltransferases. This Men1 complex promotes histone H3 lysine 4 trimethylation at target loci including homeobox genes and cyclin-dependent kinase inhibitor genes. The loss of Men1 may be tumorigenic because it leads to decreased histone H3 lysine 4 trimethylation resulting in expressional changes of specific genes. Reversing tumorigenesis induced by a Men1 deficiency might be achieved by inhibition of histone H3 lysine 4 demethylase Rbp2 (Kdm5a). To this end, pancreatic islets from Men1f|f, Rbp2f|f and Men1f|f Rbp2f|f mice were expression profiled to determine what transcriptional changes induced by a Men1 deficiency are reversed by the loss of Rpb2. Pancreatic islets were isolated from Men1flf RIP-Cre mice, Rbp2flf RIP-Cre mice, Men1flf Rbp2flf RIP-Cre mice and two month old matched control mice. Total mRNA was extracted from islets and expression profiled on microarrays.

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Cherniack

PROVIDER: E-GEOD-26978 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1.

Lin Wenchu W Cao Jian J Liu Jiayun J Beshiri Michael L ML Fujiwara Yuko Y Francis Joshua J Cherniack Andrew D AD Geisen Christoph C Blair Lauren P LP Zou Mike R MR Shen Xiaohua X Kawamori Dan D Liu Zongzhi Z Grisanzio Chiara C Watanabe Hideo H Minamishima Yoji Andrew YA Zhang Qing Q Kulkarni Rohit N RN Signoretti Sabina S Rodig Scott J SJ Bronson Roderick T RT Orkin Stuart H SH Tuck David P DP Benevolenskaya Elizaveta V EV Meyerson Matthew M Kaelin William G WG Yan Qin Q

Proceedings of the National Academy of Sciences of the United States of America 20110725 33

Aberrations in epigenetic processes, such as histone methylation, can cause cancer. Retinoblastoma binding protein 2 (RBP2; also called JARID1A or KDM5A) can demethylate tri- and dimethylated lysine 4 in histone H3, which are epigenetic marks for transcriptionally active chromatin, whereas the multiple endocrine neoplasia type 1 (MEN1) tumor suppressor promotes H3K4 methylation. Previous studies suggested that inhibition of RBP2 contributed to tumor suppression by the retinoblastoma protein (pRB ...[more]

PMID: 21788502

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Project description:To explore the underlying mechanism for the regulatory role of branched-chain amino acids (BCAA) catabolism in hypothalamic RIP-Cre neurons to metabolic organs under normal chow diet feeding, we established RIP-Cre neurons selective BCAA catabolic enzyme branched-chain ketoacid dehydrogenase E1 subunit alpha(Bckdha) knockout mice, we conducted RNA sequencing on the inguinal adipose tissue (iWAT), epididymal adipose tissues (eWAT), and liverfrom wild type (WT, Bckdhaf/f) and knockout (KO, Bckdhaf/f;RIP-Cre) mice (two groups in total). Three biological replicates were performed for each group. Methods: RNA sequencing (RNA-Seq) and data analysis were performed by Gene Denovo Biotechnology (Guangzhou, China). Results: In comparison with findings in the Bckdhaf/f group, 393 up-regulated and 214 down-regulated differentially expressed genes (DEGs) were identified in eWAT from Bckdhaf/f;RIP-Cre group . Similarly, 41 up-regulated genes and 152 down-regulated DEGs were identified in iWAT from Bckdhaf/f;RIP-Cre compared to the Bckdhaf/f group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that DEGs in eWAT were enriched in the categories including all subclass pathways in carbohydrate metabolism class, insulin resistance, PPAR signaling, oxidative phosphorylation, thermogenesis, carbon metabolism, fatty acid metabolism, biosynthesis of amino acids and degenerative disease pathways. Similarly, DEGs in iWATwere clustered in the pathways, including the TCA cycle, pyruvate metabolism, glucagon signaling, glycolysis and gluconeogenesis, and carbon metabolism. These changes indicated broad disturbance in WAT energy metabolism in Bckdhaf/f;RIP-Cre mice. Liver transcriptomes showed minor perturbances in subclasses in lipid metabolism, advanced glycation end products and their receptor (AGE-RAGE), PPAR, estrogen, prolactin signaling pathways. Notably, all 13 mitochondrial DNA encoded mRNA were all significantly down-regulated in eWAT of Bckdhaf/f;RIP-Cre mice, along with nucleus DNA encoded mitochondrial located mRNA. Conclusions: Our results using RNA-Seq indicated universal defects of mitochondrial gene expression in eWAT and iWAT.

Dataset Information

Expression data from pancreatic islets from Men1flf RIP-Cre mice, Rbp2flf RIP-Cre mice, Men1flf Rbp2flf RIP-Cre mice and matched control.

Publications

Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1.

Similar Datasets

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