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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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Selective influence of Sox2 on POU transcription factor binding in embryonic and neural stem cells

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2015-08-21 | GSE69859 | GEO

Selective Regulation of a Defined Subset of Inflammatory and Immunoregulatory Genes by an NF-kB p50-IkBz Pathway

Project description:The five NF-kB family members and three nuclear IkB proteins play diverse biological roles, but the mechanisms by which distinct NF-kB and NF-kB:IkB complexes contribute to selective gene transcription remain poorly understood. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent and IkBz-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key inflammatory and immunoregulatory genes, including Il6, Il1b, Nos2, Lcn2, and Batf, were among the p50-IkBz co-dependent genes. IkBz typically bound genomic sites occupied earlier by NF-kB dimers. However, p50-IkBz co-dependence did not coincide with the preferential binding of either protein, as p50, IkBz, and RelA co-occupied thousands of sites. A common feature of p50-IkBz co-dependent genes was close proximity to a p50/RelA/IkBz co-bound site exhibiting p50-dependent binding of RelA and IkBz. This result and others suggest that IkBz function is not restricted to p50 homodimers. Notably, IkBz and the p50-IkBz target genes comprise a high percentage of genes that exhibited the greatest differential expression between TLR4-stimulated and tumor necrosis factor receptor (TNFR)-stimulated macrophages, with ectopic IkBz rescuing a subset of these genes. These results reveal a defined p50-IkBz pathway that selectively activates a set of key inflammatory and immunoregulatory genes and serves as an important contributor to the differential responses to TNFR and TLR4.

2024-03-14 | GSE249261 | GEO

Selective Regulation of a Defined Subset of Inflammatory and Immunoregulatory Genes by an NF-kB p50-IkBz Pathway

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2024-04-23 | GSE245681 | GEO

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Nono deficiency impedes the proliferation and adhesion of H9c2 cardiomyocytes through Pi3k/Akt signaling pathway [RNA-seq

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Transcription factors harbor functional RNA-binding domains

Project description:Transcription factors (TFs) orchestrate the gene expression programs that define each cell’s identity, and the canonical TF accomplishes this with two functional domains1–7. The DNA-binding domain interacts with specific genomic sequences, and the effector domain binds coactivators or co-repressors that contribute to transcriptional regulation. We report here that TFs also frequently contain an RNA-binding domain and that this also contributes to gene regulation. Nearly half of TFs in human cells show evidence of RNA-binding and their affinities for RNA are similar to those of well-studied RNA-binding proteins. The RNA-binding sites of TFs have sequence and functional features analogous to the arginine-rich motif of the HIV transcriptional activator Tat8,9. RNA-binding contributes to TF function by promoting the dynamic association of TFs with chromatin. We conclude that the canonical definition of transcription factors is incomplete, and that the ability of many TFs to bind DNA, RNA and protein is fundamental to gene regulation.

2023-07-02 | PXD035484 | Pride

Transcription factor trapping by RNA in gene regulatory elements (GRO-Seq)

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2015-10-29 | E-GEOD-68197 | biostudies-arrayexpress

Transcription profiling of mouse fibroblasts to understand the effect of radiation on Oct-1 deficient and wild type mouse strains.

Project description:The POU-domain transcription factor Oct-1 is widely expressed in adult tissues and has been proposed to regulate a large group of target genes. Microarray expression profiling was used to evaluate gene expression changes in Oct-1-deficient mouse fibroblasts. A number of genes associated with cellular stress exhibited altered expression. Consistent with this finding, Oct-1-deficient fibroblasts were hypersensitive to radiation, doxorubicin, and hydrogen peroxide and harbored elevated reactive oxygen species. Expression profiling identified a second group of genes dysregulated in Oct-1-deficient fibroblasts following irradiation, including many associated with oxidative and metabolic stress. A number of these genes contain octamer sequences in their immediate 5' regulatory regions, some of which are conserved in human. These results indicate that Oct-1 modulates the activity of genes important for the cellular response to stress. overall experiment design: WT,WTR,MU and MUR replicates from Affymetrix GeneChip Mouse Expression Set 430 Arrays A and B

2007-09-21 | E-GEOD-2084 | biostudies-arrayexpress

Transcription factor trapping by RNA in gene regulatory elements (CLIP-Seq)

2015-10-29 | E-GEOD-68196 | biostudies-arrayexpress

Reprogramming competence of POU factors is linked to the donor-cell epigenome

Project description:Octamer-binding Pit-Oct-Unc (POU) family members have distinct reprogramming competences. OCT4 induces pluripotency, whereas POU III factors (OCT6, OCT7, OCT8, and OCT9) lack this ability, but are prone to inducing neural identities. However, which specific features of these proteins render the distinct reprograming competences remains unknown. Here, we present that OCT6 can also induce pluripotency. But, it works only with human cells, indicating its species-dependent reprogramming activity. Functional readouts with a series of reciprocal mutants uncover that the central role of OCT4 and its strong reprogramming competence to pluripotency arise from its C-terminal transactivation domain. Furthermore, we identify intrinsic properties of OCT7, OCT8, and OCT9 that are detrimental for inducing pluripotency. A chemical screen reveals that their persistent deficiency for inducing pluripotency can be surmounted by reducing H3K79 methylation in donor cells. Our findings delineate that intrinsic properties of POU factors and their responsive donor-cell epigenome state are tightly linked to the reprogramming competence.

2020-06-24 | GSE95608 | GEO

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