IκBζ target genes in chronic lymphocytic leukemia
Abstract
IκBζ, an atypical IκB protein induced downstream of Toll-like receptor (TLR) signaling, is pivotal in orchestrating inflammatory responses and modulating inflammation-associated B cell malignancies. However, the transcriptional and epigenetic programs regulated by IκBζ in both normal and malignant B cells remain poorly described. Here, we analyzed chronic lymphocytic leukemia (CLL) cells by epigenomic profiling to dissect the molecular function of IκBζ in leukemia. In primary human B cells and CLL samples, chromatin immunoprecipitation sequencing (ChIP-seq) and cleavage under targets and tagmentation (CUT&Tag) analyses delineated a comprehensive genome-wide landscape of IκBζ binding sites. Key genes, including NFKB2, BATF, and FOXP1, gained IκBζ binding after TLR stimulation in both CLL and B cells, whereas CXCR5 was mainly bound in CLL cells. Pharmacological or genetic inhibition of IκBζ signaling disrupted the induction of these molecules, highlighting its potential role as a central transcriptional tuner that integrates TLR-mediated inflammatory pathways with B cell receptor (BCR) signaling and migration.
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BibTeX
@article{sana2026iκbζ,
title = {{IκBζ target genes in chronic lymphocytic leukemia}},
author = {Ilenia Sana and Miriam Meloni and Francesca Genova and Maria Elena Mantione and Anna Sofia Tascini and Ettore Zapparoli and Greta Carbone Faccin and Dimitra Paschaloudi and Martina Del Nero and Chiara Lenzi and Pamela Ranghetti and Eleonora Perotta and Lydia Scarfò and Paolo Ghia and Marta Muzio},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117828},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03209-8},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - IκBζ target genes in chronic lymphocytic leukemia
AU - Ilenia Sana
AU - Miriam Meloni
AU - Francesca Genova
AU - Maria Elena Mantione
AU - Anna Sofia Tascini
AU - Ettore Zapparoli
AU - Greta Carbone Faccin
AU - Dimitra Paschaloudi
AU - Martina Del Nero
AU - Chiara Lenzi
AU - Pamela Ranghetti
AU - Eleonora Perotta
AU - Lydia Scarfò
AU - Paolo Ghia
AU - Marta Muzio
PY - 2026
DA - 2026/10/12
JO - iScience
DO - 10.1016/j.isci.2026.117828
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03209-8
AB - IκBζ, an atypical IκB protein induced downstream of Toll-like receptor (TLR) signaling, is pivotal in orchestrating inflammatory responses and modulating inflammation-associated B cell malignancies. However, the transcriptional and epigenetic programs regulated by IκBζ in both normal and malignant B cells remain poorly described. Here, we analyzed chronic lymphocytic leukemia (CLL) cells by epigenomic profiling to dissect the molecular function of IκBζ in leukemia. In primary human B cells and CLL samples, chromatin immunoprecipitation sequencing (ChIP-seq) and cleavage under targets and tagmentation (CUT&Tag) analyses delineated a comprehensive genome-wide landscape of IκBζ binding sites. Key genes, including NFKB2, BATF, and FOXP1, gained IκBζ binding after TLR stimulation in both CLL and B cells, whereas CXCR5 was mainly bound in CLL cells. Pharmacological or genetic inhibition of IκBζ signaling disrupted the induction of these molecules, highlighting its potential role as a central transcriptional tuner that integrates TLR-mediated inflammatory pathways with B cell receptor (BCR) signaling and migration.
SN - 2589-0042
ER -