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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Temporal mapping of C/EBPα and –β binding during liver regeneration

ABSTRACT: Temporal mapping of C/EBPα and –β binding during liver regeneration reveals dynamic occupancy and specific regulatory codes for homeostatic and cell cycle gene batteries. Timeseries ChIP-seq of transcription factors C/EBPα and –β, and Pol II in time points 0, 3, 8, 16, 24, 36, 48, 168 hours after partial hepatectomy. Additionally, an IgG mock to 0h was sequenced, as well as the transcription factor Egr1.

ORGANISM(S): Mus musculus

SUBMITTER: Johannes Waage

PROVIDER: E-GEOD-42321 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Temporal mapping of CEBPA and CEBPB binding during liver regeneration reveals dynamic occupancy and specific regulatory codes for homeostatic and cell cycle gene batteries.

Jakobsen Janus Schou JS Waage Johannes J Rapin Nicolas N Bisgaard Hanne Cathrine HC Larsen Fin Stolze FS Porse Bo Torben BT

Genome research 20130212 4

Dynamic shifts in transcription factor binding are central to the regulation of biological processes by allowing rapid changes in gene transcription. However, very few genome-wide studies have examined how transcription factor occupancy is coordinated temporally in vivo in higher animals. Here, we quantified the genome-wide binding patterns of two key hepatocyte transcription factors, CEBPA and CEBPB (also known as C/EBPalpha and C/EBPbeta), at multiple time points during the highly dynamic proc ...[more]

PMID: 23403033

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Temporal mapping of C/EBPα and –β binding during liver regeneration

Project description:Temporal mapping of C/EBPα and –β binding during liver regeneration reveals dynamic occupancy and specific regulatory codes for homeostatic and cell cycle gene batteries.

2013-01-24 | GSE42321 | GEO

A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis

Project description:We explored the connection between C/EBPα (CCAAT/enhancer binding protein α) and Wnt signaling in gut homeostasis and carcinogenesis. C/EBPα was expressed in human and murine intestinal epithelia in the transit amplifying region of the crypts and was absent in intestinal stem cells and Paneth cells with activated Wnt signaling. In human colorectal cancer and murine APCMin/+ polyps, C/EBPα was absent from nuclear β-catenin–positive tumor cells. In chemically induced intestinal carcinogenesis, C/EBPα KO in murine gut epithelia increased tumor volume. C/EBPα deletion extended the S-phase cell zone in intestinal organoids and activated typical proliferation gene expression signatures, including that of Wnt target genes. Genetic activation of β-catenin in organoids attenuated C/EBPα expression. Comparing gene expression of wild type and C/EBPα KO organoids by RNA sequencing aimed to identify C/EBPα dependent alterations in gene expression.

2018-12-24 | GSE123925 | GEO

Transcriptome profiling of wild type, K159/298Q- and K159/298R- C/EBPα expressing mouse cells

Project description:To investigate the consequences of C/EBPα-acetylation on global C/EBPα-controlled gene transcription we generated Hepa1-6 mouse hepatoma cell lines with cumate-inducible expression of wt-, K159Q/K298Q- or K159R/K298R-C/EBPα-FLAG proteins

2018-06-01 | E-MTAB-6323 | biostudies-arrayexpress

C/EBPα is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition

Project description:RNA-sequencing of human mammary epithelial cells (HMLEs) that were lentivirally transduced with vector that constitutively expresses C/EBPα and its respective empty vector control. Both lines were analyzed with and without TGF-β treatment.

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Genome-wide co-occupancy of Hoxa9 and C/EBPα in Hoxa9/Meis1 transformed HSCs [ChIP-seq]

Project description:Identification of the genome-wide binding sites of Hoxa9 and C/EBPα in a murine myeloblastic cell line transformed by Hoxa9/Meis1. Over 50% of Hoxa9 binding sites are co-bound by C/EBPα, providing mechanistic insight into the requirement of C/EBPα for Hoxa9-mediated leukemogenesis. Additionally, genome-wide occupancy of H3K4 monomethylation and H3K27 trimethylation provide additional information on the functionality of Hoxa9/C/EBPα cobound loci. Examination of two transcription factor binding sites and two histone modifications in a transformed cell line.

2014-06-11 | E-GEOD-58361 | biostudies-arrayexpress

Development of MLL-rearranged leukemia is dependent on a transcriptional program orchestradt by C/EBPα

Project description:Translocations involving the MLL genes are frequently found in Acute Myeloid Leukemia (AML) and are associated with poor prognosis. The MLL fusion proteins act as aberrant transcription factor activating a transcriptional program that transforms the cells, potentially through collaboration with other transcription factors. To investigate this we searched gene expression profiles from patients with MLL-rearranged AML compared with normal hematopoietic progenitor cells for transcriptional regulators and found targets of C/EBPα to be up-regulated in the AML samples, suggesting that C/EBPα might collaborate with MLL fusion proteins in the initial transformation process. We could show that transformation by MLL fusion proteins is dependent on C/EBPα activity both in early progenitors as well as in GMPs. In contrast, C/EBPα was found to be indispensable in an already established leukemia. These results suggest that C/EBPα play an important role in the early transforming event of leukemogenesis. We used microarray to study the early transcriptional changes induced by MLL-ENL expression and we identified a combined C/EBPα / MLL-ENL transcriptional signature. 3 Cebpaflox/flox;Mx1Cre and 3 Cebpaflox/flox;Mx1Cre- mice were sacrificed 14 days after pIpC injection and bone marrow cells were harvested, enriched for cKit-expression and transduced with a pMIG retroviral vector expressing the MLL-ENL fusion protein and GFP. 72 h post first transduction, GFP-positive or negative PreGM cells were sorted.

2013-12-10 | E-GEOD-46534 | biostudies-arrayexpress

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Project description:C/EBPα induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem cells (iPSCs) when co-expressed with Oct4, Sox2, Klf4 and Myc (OSKM). However, how C/EBPα accomplishes these effects is unclear. We now found that transient C/EBPα expression followed by OSKM activation induces a 100 fold increase in iPSC reprogramming efficiency, involving 95% of the cells. During this conversion pluripotency and epithelial-mesenchymal transition genes become dramatically up-regulated and 60% of the cells express Oct4 within 2 days. C/EBPα acts as a pathbreaker since it transiently makes the chromatin of pluripotency genes more accessible to DNase I. It also induces the expression of the dioxygenase Tet2 and promotes its translocation to the nucleus where it binds to regulatory regions of pluripotency genes that become demethylated following OSKM induction. In line with these findings, overexpression of Tet2 enhances OSKM‐induced B cell reprogramming. Since the enzyme is also required for efficient C/EBPα-induced immune cell conversion, our data suggest that Tet2 provides a mechanistic link between iPSC reprogramming and B cell transdifferentiation. The rapid iPS reprogramming approach described should help to fully elucidate the process and has potential clinical applications. Change in Cebpa genome binding/occupancy, comparing primary B-cells treated with estradiol for 18h to induce C/EBPa to untreated cells.

2013-11-17 | E-GEOD-52373 | biostudies-arrayexpress

C/EBPα and PPARγ-specific transcriptional programs in mature adipocytes in vivo

Project description:We took a systematic approach to determine the transcriptional programs that are specifically regulated by C/EBPα in mature white adipocytes of mice on chow diet or high fat diet. The hypothesis tested in the present study was that C/EBPα, as a lipogenic transcription factor, has unique direct targets compared to PPARγ. Our inducible adipocyte specific knockout system allows us to test the direct targets of C/EBPα and PPARγ in adipocytes by short-term C/EBPα or PPARγ elimination in mature adipocytes in vivo. Results indicate that although it has been shown that C/EBPα and PPARγ cross-regulate each other, they have distinct direct responsive targets. Moreover, there are very few C/EBPα specific targets in mice on a chow diet, most of the C/EBPα targets in mature adipocytes are genes modulated by HFD feeding.

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Cross-species comparison of C/EBPα and PPARγ profiles in mouse and human adipocytes reveals interdependent retention of binding sites

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Gene expression changes after loss of C/EBPα in transformed HSCs [CEBPA RNA-seq]

Project description:RNAseq characterization of gene expression changes 72 hours after genomic excision of Cebpa in murine hematopoietic progenitors from Cebpaf/f;CreER mice transformed by Hoxa9/Meis1. In the presence of tamoxifen (4OHT), Cre-ER localizes to the nucleus of cells allowing for excision of Cebpa and loss of C/EBPα protein levels. Loss of C/EBPα leads to a decrease in cellular proliferation. Examination of gene expression by RNAseq in two conditions in biological replicates.

2014-06-11 | E-GEOD-58360 | biostudies-arrayexpress

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