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Publication : Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program.

First Author  Green MR Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  7 Pages  2873-8
PubMed ID  21282644 Mgi Jnum  J:169063
Mgi Id  MGI:4939816 Doi  10.1073/pnas.1019537108
Citation  Green MR, et al. (2011) Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program. Proc Natl Acad Sci U S A 108(7):2873-8
abstractText  We utilized gene expression profiling of a comprehensive panel of purified developmentally defined normal murine B cells to identify unique transcriptional signatures for each subset. To elucidate transcription factor activities that function in a stage-specific fashion, we used gene sets that share transcription factor targets and found that germinal center B cells had a robust enrichment of up-regulated and down-regulated signatures compared with the other B-cell subsets. Notably, we found Yy1 and its targets to be central regulators of the germinal center B (GCB)-specific transcriptional program with binding of Yy1 to select signature genes in GCB cells, and translation of the Yy1 signatures to human GCB cells. We then tested whether our newly generated, stage-specific transcriptional signatures could be used to link murine lymphoma models to stages of normal B-cell development. Although each of the molecularly defined murine lymphoma models conserved certain stage-specific features of normal B-cell development, there was a significant alteration of the normal differentiation signature following malignant transformation. These findings offer important tools and insights for elucidating differences between normal and malignant B cells.
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