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Transcriptome profiling of colorectal cancer cells on BZW2 knockdown.

ABSTRACT: Basic leucine zipper and W2 domains 2 (BZW2), also known as translation initiation regulator eIF5-mimic protein 1 (5MP1), is a member of the basic‐region leucine zipper (bZIP) superfamily of transcription factors. BZW2 has partial homology with eIF5 and can function as a competitive inhibitor of eIF5. In human Colorectal cancers, high mRNA and protein expression levels of BZW2 were associated with tumor progression. BZW2-knockdown reduced malignant phenotypes, including cell proliferation, invasion, and spheroid and colony formation. BZW2-knockdown also reduced tumor growth and metastasis In summary, our study characterizes the expression BZW2 in colorectal cancer and explore its regulation mechanism. Future studies are needed to decipher the biological significance of these findings.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227069 | GEO | 2023/03/14

REPOSITORIES: GEO

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Next generation sequencing facilities quantitative analysis of negative control HCT116 cells and 5MP1-overexpressed HCT116 cells.

Project description:To investigate the downstream targets of eIF5 mimic protein 1 (5MP1), also known as Basic Leucine Zipper and W2 domains 2 (BZW2; Ensembl:ENSG00000136261), we performed a transcriptomic analysis using high throoughput RNA sequencing (RNA-seq).

2018-08-04 | GSE118105 | GEO

Genome-wide identification of bZIP29 target genes in Arabidopsis cell cultures

Project description:The Arabidopsis basic leucine zipper transcription factor bZIP29 of the bZIP group I TF family, expressed mainly in proliferative tissues, is functionally characterized in this study. Genes bound by bZIP29 were mapped genome-wide using a tandem ChIP procedure (TChAP) on cell cultures expressing the TF fused to the His-Bio-His tag. The generated data suggests that bZIP29 might be an important player in the reorganization of cell walls during cell proliferation.

2017-05-13 | E-MTAB-3754 | biostudies-arrayexpress

Genome-wide survey by ChIP-seq reveals CREB1 regulation of lncRNAs in gastric cancer.

Project description:cAMP responsive element binding protein 1 (CREB1) is a transcription factor belonging to the basic leucine zipper (bZIP) family. Previous studies on the transcriptional regulatory targets of CREB1 have focused on protein-coding genes. The non-coding targets regulated by CREB1 in gastric cancer remain to be further studied. Herein, the genome-wide mapping of CREB1 binding in gastric cancer cell AGS was determined by chromatin immunoprecipitation sequencing.

2024-01-31 | GSE220708 | GEO

Transcription profiling of mouse liver and kidney from PAR bZip triple knockout mice to wild-type or heterozygous mutant mice to identify genes contributing to the morbidity of PAR bZIP triple KO mice and circadian liver detoxification

Project description:The PAR-domain basic leucine zipper (PAR bZip) transcription factors DBP, TEF, and HLF accumulate in a highly circadian manner in several peripheral tissues, including liver and kidney. Mice devoid of all three of these proteins are born at expected Mendelian ratios, but are epilepsy-prone, age at an accelerated rate and die prematurely. In the hope of identifying PAR bZip target genes whose altered expression might contribute to the high morbidity and mortality of PAR bZip triple knockout mice, we compared the liver and kidney transcriptomes of these animals to those of wild-type or heterozygous mutant mice. These experiments revealed that PAR bZip proteins control the expression of many enzymes and regulators involved in detoxification and drug metabolism, such as cytochrome P450 enzymes, carboxylesterases, and constitutive androstane receptor (CAR). Indeed, PAR bZip triple knockout mice are hypersensitive to xenobiotic compounds, and the deficiency in detoxification may contribute to their early ageing.

2006-12-20 | E-MEXP-565 | biostudies-arrayexpress

Genome-wide transcriptome analysis bZIP29 dominant negative repressor line in root tips of Arabidopsis

Project description:The Arabidopsis basic leucine zipper transcription factor bZIP29 of the bZIP group I TF family, expressed mainly in proliferative tissues, is functionally characterized in this study. In roots, bZIP29 is highly expressed in the quiescent centre and the columella cells of the root apical meristem. Mutant analyses demonstrate that bZIP29 regulates root meristem cell number and root gravitropic responses. RNA-seq transcriptome profiling of the root meristem shows that bZIP29 target genes are linked to cell wall organization, and that gene regulatory networks controlling proper root meristem organization are intensively rewired upon its perturbation.

2016-11-07 | E-MTAB-3755 | biostudies-arrayexpress

Intricate coupling between the transactivation and basic-leucine zipper domains governs the CK2-dependent phosphorylation of ATF4

Project description:Most transcription factors possess at least one long intrinsically disordered transactivation domain that binds to a variety of co-activators and co-repressors and plays a key role in modulating the transcriptional activity. Despite the crucial importance of these mechanisms, the structural and functional basis of transactivation domain in yet poorly understood. Here, we focused on ATF4/CREB-2, an essential transcription factor for cellular stress adaptation. We found that the N-terminal region of the transactivation domain is involved in transient long-range interactions with the basic-leucine zipper domain. In vitro phosphorylation assays with the protein kinase CK2 show that the presence of the basic-leucine zipper domain is required for optimal phosphorylation of the transactivation domain. This study uncovers the intricate coupling existing between the transactivation and basic-leucine zipper domains of ATF4 and highlights its potential functional relevance.

2023-03-11 | PXD029704 | Pride

Transcription profiling of liver from wild type, Rev knock out and Rev-erb-alpha transcgenic mice to identify target genes of PAR bZip

Project description:Found PAR bZip target genes. The loss of circadian PAR bZip transcription factors results in epilepsy, DBP (albumin D-site-binding protein), HLF (hepatic leukemia factor), and TEF (thyrotroph embryonic factor) are the three members of the PAR bZip (proline and acidic amino acid-rich basic leucine zipper) transcription factor family. All three of these transcriptional regulatory proteins accumulate with robust circadian rhythms in tissues with high amplitudes of clock gene expression, such as the suprachiasmatic nucleus (SCN) and the liver. However, they are expressed at nearly invariable levels in most brain regions, in which clock gene expression only cycles with low amplitude. Here we show that mice deficient for all three PAR bZip proteins are highly susceptible to generalized spontaneous and audiogenic epilepsies that frequently are lethal. Transcriptome profiling revealed pyridoxal kinase (Pdxk) as a target gene of PAR bZip proteins in both liver and brain. Pyridoxal kinase converts vitamin B6 derivatives into pyridoxal phosphate (PLP), the coenzyme of many enzymes involved in amino acid and neurotransmitter metabolism. PAR bZip-deficient mice show decreased brain levels of PLP, serotonin, and dopamine, and such changes have previously been reported to cause epilepsies in other systems. Hence, the expression of some clock-controlled genes, such as Pdxk, may have to remain within narrow limits in the brain. This could explain why the circadian oscillator has evolved to generate only low-amplitude cycles in most brain regions.; find REV-ERB ALPHA target genes

2010-06-22 | E-TABM-726 | biostudies-arrayexpress

The Aspergillus nidulans metZ gene encodes a transcription factor involved in regulation of sulfur metabolism in this fungus and other Eurotiales

Project description:In Aspergillus nidulans, expression of sulfur metabolism genes is activated by the MetR transcription factor containing a basic region and leucine zipper domain (bZIP). Here we identified and characterized MetZ, a new transcriptional regulator in Aspergillus nidulans and other Eurotiales. It contains a bZIP domain similar to the corresponding region in MetR and this similarity suggests that MetZ could potentially complement the MetR deficiency. The metR and metZ genes are interrupted by unusually long introns. Transcription of metZ, unlike that of metR, is controlled by the sulfur metabolite repression system (SMR) dependent on the MetR protein. Overexpression of metZ from a MetR-independent promoter in a metR strain, activates transcription of genes encoding sulfate permease, homocysteine synthase and methionine permease, partially complementing the phenotype of the metR mutation. Thus, MetZ appears to be a second transcription factor involved in regulation of sulfur metabolism genes.

2015-03-23 | GSE62548 | GEO

ATF4 Promotes Skeletal Muscle Atrophy by Forming a Heterodimer with C/EBPbeta

Project description:Skeletal muscle atrophy is a highly prevalent and debilitating condition that remains poorly understood at the molecular level. Previous work found that skeletal muscle atrophy involves activating transcription factor 4 (ATF4), a protein in the basic leucine zipper (bZIP) transcription factor family. However, the direct biochemical mechanism by which ATF4 promotes muscle atrophy was unknown. Because bZIP proteins such as ATF4 must dimerize to bind and activate genes, and because ATF4 is unable to form highly stable homodimers, we hypothesized that ATF4 may promote muscle atrophy by heterodimerizing with another bZIP family member. To test this hypothesis, we biochemically isolated skeletal muscle proteins that associate with the dimerization- and DNA-binding domain of ATF4 (the bZIP domain) in mouse skeletal muscle fibers in vivo. Interestingly, we found that ATF4 makes up one half of at least 5 distinct heterodimeric bZIP transcription factors in skeletal muscle fibers. This three-way interaction between ATF4, C/EBPbeta and the ATF4-C/EBP composite site activates the Gadd45a gene, which encodes a known mediator of muscle atrophy (Gadd45a). Together, these results identify a direct biochemical mechanism by which ATF4 induces skeletal muscle atrophy and provide new insight into the way that skeletal muscle atrophy occurs at the molecular level.

2019-11-04 | MSV000084538 | MassIVE

In vitro, genomic context identification of transcription factor binding sites for bZIP C/S1 homodimers and heterodimers

Project description:In eukaryotes, many transcription factors (TF) usually form dimers or oligomers with itself or other TFs to regulate gene expression. To study how homo- and heterodimerization of TFs affect DNA binding specificity, we developed a double DNA Affinity Purification sequencing (double DAP-seq; dDAP-seq) technique that maps heterodimer binding sites in endogenous genome context and applied it to elucidate the binding profiles of homo- and heterodimers of the Group C and S1 basic leucine zipper (bZIP) transcription factors in Arabidopsis. Genome-wide binding profiles of twenty pairs of bZIP C/S1 heterodimers and bZIP S1 homodimers revealed that heterodimerization significantly expands the DNA binding preferences of homodimers, creating unique binding sites and target gene functions. In addition to the classical ACGT elements recognized by plant bZIPs, we found the Group C/S1 dimers bind to sequence motifs that might share an origin with the yeast bZIP GCN4. Further analysis of heterodimer-specific binding sequences uncovered two types of motif recognition patterns that mediate heterodimer specificity. Our study shed light on the functions and mechanisms of TF dimerization and demonstrated the potential of dDAP-seq in deciphering the complexity of these interactions within or across TF families.

2023-04-06 | GSE198873 | GEO

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