| 1. |
- Carlsson, Robert, et al.
(författare)
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Genomic structure of mouse SPI-C and genomic structure and expression pattern of human SPI-C.
- 2002
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Ingår i: Gene. - 1879-0038. ; 299:1-2, s. 271-278
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Tidskriftsartikel (refereegranskat)abstract
- Erythroblast transformation-specific domain (ETS) transcription factors regulate some of the critical molecular mechanisms controlling the differentiation of multipotent haematopoietic progenitor cells into effector B-lymphocytes. The SPI-group ETS-protein transcription factors PU.1 and SPI-B play essential and, although coexpressed and binding to similar DNA sequences, unique roles in B-cell differentiation in mice. Mouse SPI-C is an SPI-group ETS protein expressed temporarily during B-cell development and in macrophages. Here we present the genomic organization of the mouse SPI-C gene, and show by rapid amplification of cDNA ends (5′-RACE) analysis that transcription of the mouse SPI-C mRNA starts at a single site producing a single processed transcript. We have also isolated a cDNA clone encoding the human SPI-C homologue, which displays 65% amino acid identity to the murine protein. In addition, we show that the genomic structure of the human and mouse genes are similar, containing a 5′ non-coding exon followed by five coding exons. Human SPI-C mRNA is preferentially detected in foetal and adult spleen, lymph nodes and at lower levels in bone marrow and foetal liver. Finally a phylogenetic prediction analysis of SPI-group protein sequences suggest that the SPI-C proteins form a distinct subgroup, with human SPI-C being closest related to the mouse SPI-C protein.
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| 2. |
- Liberg, David
(författare)
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Regulation of immunoglobulin transcription
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Each Ig V-region has its own upstream promoter and the promoter of a mature Ig gene is thereby selected during the V(D)J recombination process. Upon comparison, it is evident that only one transcription factor binding site, the octamer, is preserved within all promoters. The octamer motif and the binding Oct-proteins are crucial for Ig promoter function, but not sufficient for a high level of transcription. We have compared mouse and human Igk promoters in detail and found that other DNA elements were conserved between subgroups of V regions. This was true also between related mouse and human subgroups. To study Ig promoter function, we have used the SP6 k promoter as a model promoter. This promoter contains several sites that are conserved in certain Igk promoter subgroups, in addition to the octamer. The promoter is dependent on a functional octamer but needs the other regions to stimulate transcription at a high level. Mutations of the octamer that lowered the affinity for Oct-proteins were functionally compensated for by the surrounding regions of the SP6 k promoter, indicating that Oct-proteins are qualitative, rather than quantitative, regulators of Igk promoter function. In the region between the octamer and TATA-box we could detect two octamer-dependent costimulatory regions, A and B, centered around a CCCT-motif and an E-box. Two proteins, FA and FB, were found to bind the sequences and the A region functioned in a differentiation-specific manner. Ig transcription is also dependent on NFkB. NFkB is an attractive drug target and we used its role in Ig transcription to test six different N-substituted benzamides for NFkB-inhibitory properties. Using a model system based on the 70Z/3 cell line, we could show that compounds with a N-acetyl substitution were able to interfere with NFkB and that a chloride substitution also gave apoptosis-inducing properties.
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| 3. |
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| 4. |
- Tsapogas, Panagiotis, et al.
(författare)
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RNA analysis of B cell lines arrested at defined stages of differentiation allows for an approximation of gene expression patterns during B cell development
- 2003
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Ingår i: Journal of Leukocyte Biology. - : Society for Leukocyte Biology. - 0741-5400 .- 1938-3673. ; 74:1, s. 102-110
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Tidskriftsartikel (refereegranskat)abstract
- The development of a mature B lymphocyte from a bone marrow stem cell is a highly ordered process involving stages with defined features and gene expression patterns. To obtain a deeper understanding of the molecular genetics of this process, we have performed RNA expression analysis of a set of mouse B lineage cell fines representing defined stages of B cell development using Affymetrix(TM) microarrays. The cells were grouped based on their previously defined phenotypic features, and a gene expression pattern for each group of cell. lines was established. The data indicated that the cell lines representing a defined stage generally presented a high similarity in overall expression profiles. Numerous genes could be identified as expressed with a restricted pattern using dCHIP-based, quantitative comparisons or presence/absence-based, probabilistic state analysis. These experiments provide a model for gene expression during B cell development, and the correctly identified expression patterns of a number of control genes suggest that a series of cell fines can be useful tools in the elucidation of the molecular genetics of a complex differentiation process.
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| 5. |
- Åkerblad, Peter, et al.
(författare)
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Early B-cell factor (o/e-1) is a promoter of adipogenesis and involved in control of genes important for terminal adipocyte differentiation.
- 2002
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Ingår i: Molecular and Cellular Biology. - 0270-7306. ; 22:22, s. 8015-8025
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Tidskriftsartikel (refereegranskat)abstract
- Olf-1/early B-cell factor (O/E-1) is a transcription factor important for B-lymphocyte and neuronal gene regulation. Here we report that all three known O/E genes (O/E-1, -2, and -3) are expressed in mouse adipose tissue and are upregulated during adipocyte differentiation. Forced expression of O/E-1 in either the preadipocyte cell line 3T3-L1 or mouse embryonic fibroblasts augmented adipogenesis, and constitutive expression of O/E-1 in uncommitted NIH 3T3 fibroblasts led to initiation of adipocyte differentiation. Furthermore, a dominant negative form of O/E-1 partially suppressed 3T3-L1 adipogenesis, indicating that expression from endogenous O/E target genes is required for 3T3-L1 terminal differentiation. Thus, our data point to the importance of O/E target genes for adipocyte differentiation and suggest a novel role for O/E-1 as an initiator and stimulator of adipogenesis.
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