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The E26 Transformation-Specific-Family Transcription Factor Spi-C Is Dynamically Regulated By External Signals In B Cells, Hannah L. Raczkowski
The E26 Transformation-Specific-Family Transcription Factor Spi-C Is Dynamically Regulated By External Signals In B Cells, Hannah L. Raczkowski
Electronic Thesis and Dissertation Repository
Spi-C is an E26 transformation-specific transcription factor closely related to PU.1 and Spi-B. Spi-C has lineage-instructive functions important in antibody-generating responses, B cell development, and red pulp macrophage generation. Spi-C is inducible by heme- and NF-κB-dependent pathways in macrophages. The present research aimed to examine the regulation of Spi-C in B cells. RT-qPCR revealed that Spic expression was reduced in B cells following addition of lipopolysaccharide, anti-IgM antibodies, CD40L, or cytokines BAFF+IL-4+IL-5. Blocking proliferative signaling partially prevented downregulation of Spic. Unstimulated B cells upregulated Spic over time. To determine the mechanism of Spic regulation, we examined the Spic promoter …
The E26 Transformation-Specific Transcription Factors Pu.1, Spi-B, And Spi-C Regulate Transcriptional Activation And Repression Of Nfkb1 To Control B Cell Development And Function, Stephen Ka Ho Li
Electronic Thesis and Dissertation Repository
PU.1, Spi-B, and Spi-C are highly related E26 transformation-specific family transcription factors that can bind nearly identical DNA sequences. PU.1 and Spi-B (encoded by Spi1 and Spib respectively) are important for B cell development and function, but the function of Spi-C (encoded by Spic) in B cells is not clear. The objective of this study was to determine PU.1, Spi-B, and Spi-C’s function during B cell development, and during TLR-mediated responses. It was hypothesized that PU.1 and Spi-B were required for positively regulating components of TLR responses, and Spi-C inhibited PU.1 and Spi-B targets. Spi1+/-Spib-/- ( …
Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto
Gene Repression And Cell Cycle Regulation By Pu.1 In Acute Myeloid Leukemia, Rachel Gh Ziliotto
Electronic Thesis and Dissertation Repository
Acute myeloid leukemia (AML) is associated with mutations or chromosomal translocations in genes encoding transcription factors. PU.1 is a transcription factor that is required for the development of nearly all white blood cell types of the immune system, including B cells, granulocytes, and monocytes. Mutation of the gene encoding PU.1, SPI1 in humans and Sfpi1 in mice, is associated with AML. We hypothesized that reduced expression of PU.1 in Sfpi1BN/BNmyeloid cells will result in the development of AML in transplanted mice due to reduced repression of E2F1, leading to deregulation of the cell cycle. Results indicate that NOD/SCID/γc …