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IκBζ is a dual-use coactivator of NF-κB and POU transcription factors

ABSTRACT: OCA-B, OCA-T1, and OCA-T2 belong to a family of transcriptional coactivators that bind to POU transcription factors (TFs) to regulate gene expression in immune cells. Here, we identify IkBz (encoded by the NFKBIZ gene) as the fourth member of the OCA protein family. While originally discovered as an inducible regulator of NFkB, we show here that IkBz shares a microhomology with OCA proteins and uses this segment to simultaneously bind to POU transcription factors and octamer motif-containing DNA. Our functional reporter assays suggest that IkBz requires its interaction with POU TFs to coactivate immune-related genes. This finding is reinforced by our epigenomic analysis of MYD88 L265P-mutant lymphoma cells, which revealed colocalization of IkBz, the POU transcription factor OCT2, and NFkB:p50 at hundreds of DNA elements harboring octamer and kB motifs. These results suggest that IkBz is a transcriptional coactivator that integrates and amplifies the output of NFkB and POU transcription factors at inducible genes in immune cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239374 | GEO | 2024/01/09

REPOSITORIES: GEO

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