Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide identification of Ikaros binding sites in primary pre-B cells

ABSTRACT: Ikaros DNA binding proteins are important regulators of haematopoiesis and genetic deletion of Ikaros results in severe developmental disturbances, including delayed thymocyte differentiation and an early and complete block in B cell development. Although Ikaros ChIP-seq data are available for mouse thymocytes and human haematopoietic progenitors, it has not been achieved in B cell progenitors. The goal of this study was to identify Ikaros binding sites in pre-B cells to define Ikaros target genes which could explain the essential role of Ikaros proteins in B cell differentiation. We carried out chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) with antibodies to the C-terminus of endogenous Ikaros in primary pre-B cells isolated from mouse fetal livers.

ORGANISM(S): Mus musculus

SUBMITTER: Gopuraja Dharmalingam

PROVIDER: E-GEOD-42462 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.

Ferreirós-Vidal Isabel I Carroll Thomas T Taylor Benjamin B Terry Anna A Liang Ziwei Z Bruno Ludovica L Dharmalingam Gopuraja G Khadayate Sanjay S Cobb Bradley S BS Smale Stephen T ST Spivakov Mikhail M Srivastava Prashant P Petretto Enrico E Fisher Amanda G AG Merkenschlager Matthias M

Blood 20130109 10

Ikaros family DNA-binding proteins are critical regulators of B-cell development. Because the current knowledge of Ikaros targets in B-cell progenitors is limited, we have identified genes that are bound and regulated by Ikaros in pre-B cells. To elucidate the role of Ikaros in B-cell lineage specification and differentiation, we analyzed the differential expression of Ikaros targets during the progression of multipotent to lymphoid-restricted progenitors, B- and T-cell lineage specification, an ...[more]

PMID: 23303821

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Project description:The main goal of the project is to develop a new generation of bioinformatics resources for the integrative analysis of multiple types of 'omics data. These resources include both novel statistical methodologies as well as user-friendly software implementations. STATegra methods address many aspects of the 'omics data integration problem such as the design of multi-omics experiments, integrative transcriptional and regulatory networks, integrative variable selection, data fusion, integration of public domain data, and integrative pathway analysis. To support method development STATegra uses a model biological system, namely the differentiation process of mouse pre-B-cells. The STATegra consortium generated data focused on a critical step in the differentiation of B lymphocytes, which are key components of the adaptive immune system. Transcription factors of the Ikaros family are central to the normal differentiation of B cell progenitors and their expression increases in response to developmental stage-specific signals to terminate the proliferation of B cell progenitors and to initiate their differentiation. In particular, a novel biological system that models the transition from the pre-BI stage to the pre-BII subsequent stage, where B cell progenitors undergo growth arrest and differentiation, was used. The approach involves a pre-B cell line, B3, and an inducible version of the Ikaros transcription factor, Ikaros-ERt2. Ikaros factors act to down-regulate genes that drive proliferation and to simultaneously up-regulate the expression of genes that promote the differentiation of B cell progenitors. Hence, in the B3 system, before induction of Ikaros, cells proliferate and their gene expression pattern is similar to proliferating B cell progenitors in vivo. Following Ikaros induction, B3 cells undergo gene expression changes that resemble those that occur in vivo during the transition from cycling to resting pre-B cells, followed by a marked reduction in cellular proliferation and by G1 arrest. On this system the consortium has created a high-quality data collection consisting of a replicated time course using seven different 'omics platforms: RNA-seq, miRNA-seq, ChIP-seq, DNase-seq, Methyl-seq, proteomics and metabolomics, which is used to assess and to validate STATegra methods. The STATegra experimental design consists of a 6 point time course that captures the differentiation of B3 cells containing Ikaros-ERt2 upon Ikaros induction within a 24 hr period. The process was sampled at 0, 2, 6, 12, 18, and 24 hrs respectively after Ikaros induction by Tamoxifen. As control, B3 cells transfected with an empty vector were treated and sampled in the same way as the inducible line. Eight different 'omic technologies were measured on this system: RNA-seq, miRNA-seq, DNase-seq, RRBS-seq, ChIP-seq, scRNA-seq, Proteomics and Metabolomics. Generally, three biological replicates were obtained per platform and were processed as independent batches. Metabolomics analysis was performed using 4 biological batches (7, 8, 9 and 10) and at times 0, 2, 6, 12, 18 and 24 hrs respectively. Each sample was analyzed using gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS).

Project description:"The main goal of the project is to develop a new generation of bioinformatics resources for the integrative analysis of multiple types of omics data. These resources include both novel statistical methodologies as well as user-friendly software implementations. STATegra methods address many aspects of the omics data integration problem such as the design of multiomics experiments, integrative transcriptional and regulatory networks, integrative variable selection, data fusion, integration of public domain data, and integrative pathway analysis. To support method development STATegra uses a model biological system, namely the differentiation process of mouse pre-B-cells. The STATegra consortium generated data focused on a critical step in the differentiation of B lymphocytes, which are key components of the adaptive immune system. Transcription factors of the Ikaros family are central to the normal differentiation of B cell progenitors and their expression increases in response to developmental stage-specific signals to terminate the proliferation of B cell progenitors and to initiate their differentiation. In particular, a novel biological system that models the transition from the pre-BI stage to the pre-BII subsequent stage, where B cell progenitors undergo growth arrest and differentiation, was used. The approach involves a pre-B cell line, B3 , and an inducible version of the Ikaros transcription factor, Ikaros-ERt2. Ikaros factors act to down-regulate genes that drive proliferation and to simultaneously up-regulate the expression of genes that promote the differentiation of B cell progenitors. Hence, in the B3 system, before induction of Ikaros, cells proliferate and their gene expression pattern is similar to proliferating B cell progenitors in vivo. Following Ikaros induction, B3 cells undergo gene expression changes that resemble those that occur in vivo during the transition from cycling to resting pre-B cells, followed by a marked reduction in cellular proliferation and by G1 arrest. On this system the consortium has created a high-quality data collection consisting of a replicated time course using seven different omics platforms: RNA-seq, miRNA-seq, ChIP-seq, DNase-seq, Methyl-seq, proteomics and metabolomics, which is used to assess and to validate STATegra methods."

Dataset Information

Genome-wide identification of Ikaros binding sites in primary pre-B cells

Publications

Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.

Similar Datasets

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