title: Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program.
abstract: 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.
authors.affiliation: The Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Green
authors.forename: Stefano
authors.initials: S
authors.lastname: Monti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dalla-Favera
authors.forename: Laura
authors.initials: L
authors.lastname: Pasqualucci
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Walsh
authors.forename: Marc
authors.initials: M
authors.lastname: Schmidt-Supprian
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.forename: Donna S
authors.initials: DS
authors.lastname: Neuberg
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Todd R
authors.initials: TR
authors.lastname: Golub
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Alt
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Shipp
authors.forename: John P
authors.initials: JP
authors.lastname: Manis
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D047369:Chromatin Immunoprecipitation; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology*; D018858:Germinal Center / Q000378:metabolism*; D006801:Humans; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D050986:YY1 Transcription Factor / Q000378:metabolism*
chemical_list: D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse