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

Alpsoy, Aktan, Wu, Xiaoli S, Pal, Sujay, Klingbeil, Olaf, Kumar, Pramod, El Demerdash, Osama, Nalbant, Benan, Vakoc, Christopher R (January 2024) IκBζ is a dual-use coactivator of NF-κB and POU transcription factors. Molecular Cell. S1097-2765(24)00008. ISSN 1097-2765 (Public Dataset)

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Abstract

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 IκBζ (encoded by the NFKBIZ gene) as an additional coactivator of POU TFs. Although originally discovered as an inducible regulator of NF-κB, we show here that IκBζ 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 IκBζ requires its interaction with POU TFs to coactivate immune-related genes. This finding is reinforced by epigenomic analysis of MYD88L265P-mutant lymphoma cells, which revealed colocalization of IκBζ with the POU TF OCT2 and NF-κB:p50 at hundreds of DNA elements harboring octamer and κB motifs. These results suggest that IκBζ is a transcriptional coactivator that can amplify and integrate the output of NF-κB and POU TFs at inducible genes in immune cells.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Wu, Xiaoli Klingbeil, Olaf El Demerdash, Osama Vakoc, Christopher R. Alpsoy, Aktan Pal, Sujay Kumar, Pramod Nalbant, Benan
Communities:	CSHL labs > Vakoc lab
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	24 January 2024
Date Deposited:	08 Feb 2024 13:48
Last Modified:	15 Feb 2024 15:46
Related URLs:	Publisher
Dataset ID:	GEO: GSE239374 https://doi.org/10.17632/4xm52ybv3g.1
URI:	https://repository.cshl.edu/id/eprint/41432

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