Notch signaling induces a transcriptionally permissive state at the Complement C3d Receptor 2 (CR2) promoter in a pre-B cell model. (December 2020)

• Record Type: Journal Article
• Authors: Ng, Han Leng; Taylor, Rhonda L.; Cheng, Jessica; Abraham, Lawrence J.; Quail, Elizabeth; Cruickshank, Mark N.; Ulgiati, Daniela
• Is Part Of: Molecular immunology. Volume 128(2020:Dec.)
• Page Start: 150
• Page End: 164
• Publication Date: 2020-12
• Subjects: ALL acute lymphoblastic leukemia -- BCR B cell receptor -- ChART-PCR chromatin accessibility real-time PCR -- ChIP chromatin immunoprecipitation -- CR2 Complement Receptor 2 -- CRS CR2 intronic silencer -- DAPT N-[N-35-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester -- EMSA electrophoretic mobility shift assay -- HPLC high performance liquid chromatography -- NIC Notch intracellular domain -- qPCR real-time quantitative PCR -- SLE systemic lupus erythematosus -- UMOD Uromodulin -- β2m β-2-microglobulin; B cells -- Complement -- Gene regulation -- Human -- Molecular biology -- Transcription factors; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2020.10.001
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: CR2 is uniquely expressed on mature B cells. Notch signals induce CR2 mRNA expression in human pre-B cell line model. Following Notch signaling, dynamic chromatin changes observed within CR2 promoter. Notch signals change CR2 promoter from closed to transcriptionally permissive. Abstract: During mammalian lymphoid development, Notch signaling is necessary at multiple stages of T lymphopoiesis, including lineage commitment, and later stages of T cell effector differentiation. In contrast, outside of a defined role in the development of splenic marginal zone B cells, there is conflicting evidence regarding whether Notch signaling plays functional roles in other B cell sub-populations. Complement receptor 2 (CR2) modulates BCR-signaling and is tightly regulated throughout differentiation. During B lymphopoiesis, CR2 is detected on immature and mature B cells with high surface expression on marginal zone B cells. Here, we have explored the possibility that Notch regulates human CR2 transcriptional activity using in vitro models including a co-culture system, co-transfection gene reporters and chromatin accessibility assays. We provide evidence that Notch signaling regulates CR2 promoter activity in a mature B cell line, as well as the induction of endogenous CR2 mRNA in a non-expressing pre-B cell line. The dynamics of endogenous gene activation suggests additional unidentified factors are required to mediate surface CR2 expression on immature and mature B lineage cells.