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P52:ETS1: a transcriptional complex essential for germinal center formation [RNA_Seq_preGCB]

ABSTRACT: It is well-established that the five transcription factors of the NFκB family form homo/hetero dimers amongst themselves to regulate gene expression by binding DNA. Our study challenges this paradigm by showing that p52 activates transcription without directly binding DNA but as part of a hetero-tetrameric partnership with ETS1, a transcription factor outside the NFκB family. By generating a knock-in mouse model (p52ki/ki) with three mutated residues on p52 required for its interactions with ETS1 but not with RelB, we demonstrate that the p52:ETS1 complex is the hitherto undiscovered regulator of transcription factors, OCT1 and OBF1, known to be critical for the germinal centre (GC) program. Consequently B cell-intrinsic expression of p52:ETS1 complex is indispensable for splenic GC B cell formation and T cell-dependent antibody responses. Functionally, loss of p52:ETS1 interaction led to diminished antigen-specific IgE thereby protecting mice from allergic responses. Collectively, our expand our current knowledge of NFkB signalling and provide new therapeutic targets for the treatment of allergic diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE300336 | GEO | 2025/07/26

REPOSITORIES: GEO

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p52:ETS1: a transcriptional complex essential for germinal center formation [RNA_Seq_GCB]

Project description:It is well-established that the five transcription factors of the NFκB family form homo/hetero dimers amongst themselves to regulate gene expression by binding DNA. Our study challenges this paradigm by showing that p52 activates transcription without directly binding DNA but as part of a hetero-tetrameric partnership with ETS1, a transcription factor outside the NFκB family. By generating a knock-in mouse model (p52ki/ki) with three mutated residues on p52 required for its interactions with ETS1 but not with RelB, we demonstrate that the p52:ETS1 complex is the hitherto undiscovered regulator of transcription factors, OCT1 and OBF1, known to be critical for the germinal centre (GC) program. Consequently B cell-intrinsic expression of p52:ETS1 complex is indispensable for splenic GC B cell formation and T cell-dependent antibody responses. Functionally, loss of p52:ETS1 interaction led to diminished antigen-specific IgE thereby protecting mice from allergic responses. Collectively, our expand our current knowledge of NFkB signalling and provide new therapeutic targets for the treatment of allergic diseases.

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