I k B ζ is a dual-use coactivator of NFk B and POU transcription factors

Date

2024-03-01

Author

Alpsoy, Aktan
Wu, Xiaoli S.
Pal, Sujay
Klingbeil, Olaf
Kumar, Pramod
Demerdash, Osama El
Nalbant, Benan
Vakoc, Christopher R.

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OCA-B, OCA-T1, and OCA-T2 belong to a family of coactivators that bind to POU transcription factors (TFs) to regulate gene expression in immune cells. Here, we identify IkB zeta (encoded by the NFKBIZ gene) as an additional coactivator of POU TFs. Although originally discovered as an inducible regulator of NF-kB, we show here that IkB zeta shares a microhomology with OCA proteins and uses this segment to bind to POU TFs and octamer-motif-containing DNA. Our functional experiments suggest that IkB zeta requires its interaction with POU TFs to coactivate immune -related genes. This finding is reinforced by epigenomic analysis of MYD88 L265P - mutant lymphoma cells, which revealed colocalization of IkB zeta with the POU TF OCT2 and NF-kB:p50 at hundreds of DNA elements harboring octamer and kB motifs. These results suggest that IkB zeta is a transcriptional coactivator that can amplify and integrate the output of NF-kB and POU TFs at inducible genes in immune cells.

URI

https://hdl.handle.net/11511/116774

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Department of Biology, Article