title: Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells.
abstract: Complement receptor 2 (CR2/CD21) is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at B-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature B cells, CR2/CD21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-B versus mature B-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional B-cell window.
authors: School of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, WA, Australia.|Biochemistry and Molecular Biology, School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia.
authors: Rhonda L
authors: RL
authors: Taylor
authors: Telethon Kids Institute, The University of Western Australia, Crawley, WA, Australia.
authors: Mark N
authors: MN
authors: Cruickshank
authors: Biochemistry and Molecular Biology, School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia.
authors: Mahdad
authors: M
authors: Karimi
authors: School of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, WA, Australia.
authors: Han Leng
authors: HL
authors: Ng
authors: Biochemistry and Molecular Biology, School of Chemistry and Biochemistry, The University of Western Australia, Crawley, WA, Australia.
authors: Elizabeth
authors: E
authors: Quail
authors: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.|US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
authors: Kenneth M
authors: KM
authors: Kaufman
authors: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.|US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
authors: John B
authors: JB
authors: Harley
authors: School of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, WA, Australia.
authors: Lawrence J
authors: LJ
authors: Abraham
authors: Division of Rheumatology, Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
authors: Betty P
authors: BP
authors: Tsao
authors: Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, USA.
authors: Susan A
authors: SA
authors: Boackle
authors: School of Pathology and Laboratory Medicine, Centre for Genetic Origins of Health and Disease, The University of Western Australia, Crawley, WA, Australia.
authors: Daniela
authors: D
authors: Ulgiati
mesh_terms: D001483:Base Sequence; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007438:Introns; D020014:K562 Cells; D008969:Molecular Sequence Data; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017464:Receptors, Complement 3d / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D019013:CD40 Antigens; C508598:IL4 protein, human; D017464:Receptors, Complement 3d; D015847:Interleukin-4
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