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An enhancer in the middle of the Igκ locus orchestrates nuclear architecture to generate a diverse antigen receptor repertoire

ABSTRACT: An enhancer in the middle of the Igκ locus orchestrates nuclear architecture to generate a diverse antigen receptor repertoire

PROVIDER: PRJNA496404 | ENA |

REPOSITORIES: ENA

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An enhancer in the middle of the Igκ locus orchestrates nuclear architecture to generate a diverse antigen receptor repertoire

Project description:Purpose:The goal of this study is to assess transcriptome profile in the absence of a potent enhancer located in the V gene region of the Igκ locus in cell lines and mice Methods: RNAseq from CD19+ cells from B6.RAG1-/- and E88-/-.RAG1-/- mice. RNAseq from 445.3, wild-type (WT) and E88-/-, pro-B cell lines

2018-11-15 | GSE121224 | GEO

A B-Cell-Specific Enhancer Orchestrates Nuclear Architecture to Generate a Diverse Antigen Receptor Repertoire.

Project description:The genome is organized into topologically associated domains (TADs) that enclose smaller subTADs. Here, we identify and characterize an enhancer that is located in the middle of the V gene region of the immunoglobulin kappa light chain (Igκ) locus that becomes active preceding the stage at which this locus undergoes V(D)J recombination. This enhancer is a hub of long-range chromatin interactions connecting subTADs in the V gene region with the recombination center at the J genes. Deletion of this element results in a highly altered long-range chromatin interaction pattern across the locus and, importantly, affects individual V gene utilization locus-wide. These results indicate the existence of an enhancer-dependent framework in the Igκ locus and further suggest that the composition of the diverse antibody repertoire is regulated in a subTAD-specific manner. This enhancer thus plays a structural role in orchestrating the proper folding of the Igκ locus in preparation for V(D)J recombination.

| S-EPMC6610861 | biostudies-literature

Gene expression of polyoma middle T antigen induced mammary tumors

Project description:This SuperSeries is composed of the following subset Series: GSE30864: Gene expression of polyoma middle T antigen induced mammary tumors [AKXD x PyMT] GSE30865: Gene expression of polyoma middle T antigen induced mammary tumors [NZB x PyMT] GSE31223: Gene expression of polyoma middle T antigen induced mammary tumors [RNA_Seq : MOLF x PyMT] Refer to individual Series

2011-07-21 | E-GEOD-30866 | biostudies-arrayexpress

Transformation of enriched mammary cell populations with Polyoma Middle T Antigen influences tumor subtype and metastatic potential

Project description:Breast cancer is a multifaceted disease, exhibiting significant molecular, histological, and pathological diversity. Factors that impact this heterogeneity are poorly understood; however, transformation of distinct normal cell populations of the breast may generate different tumor phenotypes. Our previous study demonstrates that the polyomavirus middle T antigen (PyMT) oncogene can establish diverse tumor subtypes when broadly expressed within mouse mammary epithelial cells. Herein, we assess the molecular, histological, and metastatic outcomes from distinct mammary cell populations transformed with PyMT. By combining several methodologies, including lentiviral infection, cell sorting, and transplantation, we have characterized tumors arising from enriched populations of mammary epithelial cells. We have found that expression of PyMT within different cell populations influences tumor histology, molecular subtype, and metastatic potential. 32 samples, 1 from each of 32 mouse mammary tumors arising from transplanted mouse mamary epithelial cells (MMECs) transduced with PyMT-expressing lentivirus. MMECs were sorted into four different types prior to transplant: luminal CD133+ (8 samples), luminal CD133- (11 samples), stem (6 samples), and basal (7 samples). The background for the cell donor and transplant recipients mice was FVB/NJ obtained from Jackson Laboratories.

2015-09-08 | E-GEOD-64453 | biostudies-arrayexpress

Mediator orchestrates PIC assembly

Project description:Mediator orchestrates PIC assembly

| PRJEB7387 | ENA

A Diverse Lipid Antigen-Specific TCR Repertoire Is Clonally Expanded during Active Tuberculosis.

Project description:Human T cells that recognize lipid Ags presented by highly conserved CD1 proteins often express semi-invariant TCRs, but the true diversity of lipid Ag-specific TCRs remains unknown. We use CD1b tetramers and high-throughput immunosequencing to analyze thousands of TCRs from ex vivo-sorted or in vitro-expanded T cells specific for the mycobacterial lipid Ag, glucose monomycolate. Our results reveal a surprisingly diverse repertoire resulting from editing of germline-encoded gene rearrangements analogous to MHC-restricted TCRs. We used a distance-based metric (TCRDist) to show how this diverse TCR repertoire builds upon previously reported conserved motifs by including subject-specific TCRs. In a South African cohort, we show that TCRDist can identify clonal expansion of diverse glucose monomycolate-specific TCRs and accurately distinguish patients with active tuberculosis from control subjects. These data suggest that similar mechanisms govern the selection and expansion of peptide and lipid Ag-specific T cells despite the nonpolymorphic nature of CD1.

| S-EPMC6057832 | biostudies-literature

Transformation of enriched mammary cell populations with Polyoma Middle T Antigen influences tumor subtype and metastatic potential

2015-09-08 | GSE64453 | GEO

Flexible chromatin loops in the VH gene region of the Igh locus facilitate the generation of a diverse antibody repertoire

Project description:The immunoglobulin heavy-chain (Igh) locus undergoes large-scale contraction in pro-B cells, which facilitates VH-DJH recombination by juxtaposing distal VH genes next to the DJH- rearranged gene segment in the proximal Igh domain. By high-resolution mapping of long-range interactions, we now demonstrate that an array of local interaction domains establishes the three- dimensional structure of the extended Igh locus in lymphoid progenitors and thymocytes. In pro- B cells, these local domains engage in long-range interactions across the entire Igh locus, which depend on the transcription factors Pax5, YY1 and CTCF. The large VH gene cluster thereby undergoes flexible long-range interactions with the more rigidly structured 3M-bM-^@M-^Y proximal domain, which ensures that all VH genes can participate with similar probability in VH-DJH recombination to generate a diverse antibody repertoire. Notably, these long-range interactions appear to be an intrinsic feature of the VH gene cluster, as they are still generated upon mutation of the EM-NM-< enhancer, IGCR1 insulator or 3M-bM-^@M-^Y regulatory region present in the 3M-bM-^@M-^Y proximal Igh domain. 4C sequencing from mutliple celltypes with multiple viewpoints; uneven number of replicates ChIP-Seq

2013-09-30 | E-GEOD-43008 | biostudies-arrayexpress

Gene expression of polyoma middle T antigen induced mammary tumors

Project description:Gene expression of polyoma middle T antigen induced mammary tumors

| PRJNA144277 | ENA

Consequences of sEH deletion in the polyoma middle T (PyMT) breast cancer tumor proteome

Project description:The aim of this investigation was to study the consequences of interfering with soluble epoxide hydrolase (sEH) expression on tumor growth and metastasis in genetically modified animals that spontaneously generate tumors without the exogenous application of high concentrations of epoxide mediators or inhibitors. Therefore, breast cancer development was studied in mice expressing the polyoma middle T oncogene (PyMT) under the control of the mouse mammary tumor virus promoter, to induce spontaneous mammary tumors. To facilitate the study of endogenous sEH activity in tumor growth, PyMT mice were then crossed with sEH-/- mice to generate sEH-deficient mice that spontaneously generate breast tumors (so called PyMTsEH mice). For these analyses, primary tumors were removed from 20 week old mice.

2021-09-14 | PXD026214 | Pride

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