Disease relevance of ZNF167

• AP3 transcription was induced by transformation of leaf protoplasts with a transformation vector that expressed a TF(ZF) consisting of the ZFP fused to the tetrameric repeat of herpes simplex VP16's minimal activation domain [1].
• The potential therapeutic relevance of ZFP-mediated VEGF-A repression was addressed using the highly tumorigenic glioblastoma cell line U87MG [2].
• We show here that this engineered ZFP-TF activates VEGF-A in appropriate cells in culture and that the secreted VEGF-A protein induced by the ZFP protects neuroblastoma cell lines from a serum starvation insult in vitro [3].
• The ZFP phage display library strategy disclosed here, coupled with the growing availability of genome sequencing information, provides a route to identifying gene-regulating TFZFs without the prerequisite of well-defined promoter elements [4].
• Point mutations in the zinc fingers associated with Denys-Drash syndrome have dramatically different effects on the interaction of WT1-ZFP with DNA, but a consistent and modest effect on the interaction with RNA [5].

High impact information on ZNF167

• We show that the corepressor KAP-1, via its PHD (plant homeodomain) and bromodomain, links the superfamily of Krüppel associated box (KRAB) zinc finger proteins (ZFP) to the NuRD complex [6].
• These data suggest the KRAB-ZFP superfamily of repressors functions to target the histone deacetylase and chromatin remodeling activities of the NuRD complex to specific gene promoters in vivo [6].
• Although the transcription of members of this KRAB-ZFP gene subgroup is detectable in all human tissues, their expression is significantly higher in human T lymphoid cells [7].
• We found that by directly regulating zinc-finger protein (ZFP) activity, we could circumvent difficulties encountered in the generation of cell lines stably expressing conventional unregulated activators [8].
• We determined the specificity of repression by using DNA microarrays and found that the ZFP TF repressed a single gene (CHK2) within the monitored genome in two different cell types [9].

Biological context of ZNF167

• Here we report that a ZFP TF can repress target gene expression with single-gene specificity within the human genome [9].
• Thus, engineered ZFP TFs are shown to be potent regulators of gene expression with therapeutic promise in the treatment of disease [2].
• Synthetic zinc finger protein (ZFP) transcription factors were designed to target DNA sequences contained within the DNase I-hypersensitive regions [10].
• We present evidence for an enhanced activation of VEGF-A gene transcription by ZFP transcription factors fused to VP16 and p65 targeted to two distinct chromosomal sites >500 base pairs upstream or downstream of the transcription start site [10].
• Furthermore, amino acid substitutions within the HMT that ablate its catalytic activity effectively eliminate the ability of the ZFP fusions to repress transcription [11].

Anatomical context of ZNF167

• Among these 360 ZFPs, a novel ZFP cDNA named HFHZ (human fetal heart ZFP) with sequence homology to a Kruppel-associated box (KRAB) was identified [12].
• For the estimated cerebral perfusion pressure and the ZFP, established formulae were used which utilized instantaneous values of arterial pressure and middle cerebral artery flow velocity [13].

Associations of ZNF167 with chemical compounds

• Seven types of zinc finger protein (ZFP) genes based on the combinations of cysteine and histidine residues were found in a human heart cDNA database [12].
• Neurotoxic studies have shown that heavy metals directly inhibit the DNA binding of ZFP and result in adverse cellular effects [14].
• The ZFP increased significantly with ephedrine (from 29 (10) to 44 (11) mm Hg) and dobutamine (from 35 (14) to 43 (10) mm Hg) but not dopexamine (from 3 (23) to 11 (22) mm Hg) [13].
• The receptors expressed in this system, in response to ZFP expression, were functional in calcium mobilization studies and the potency of the agonists investigated was consistent with their action at CCK2 receptors (CCK-8S pA50 = 9.05+/-0.11, pentagastrin pA50 = 9.11+/-0.13) [15].
• The RT-PCR assay revealed that ZFP 15 mRNA was not regulated by cold, salt, drought and ABA stresses, though CRT/DRE and ABRE elements were found in the promoter region of ZFP 15 gene [16].

Analytical, diagnostic and therapeutic context of ZNF167

• As a result of studies with the six-finger proteins, the specific region of the promoter most accessible to transcriptional control by VP64-ZFP and KRAB-ZFP fusion proteins was elucidated and confirmed by DNaseI footprinting, flow cytometric analysis and immunofluorescence [4].
• The role of RNA sequence and secondary structure in the binding of WT1-ZFP was probed by site-directed mutagenesis [5].
• The expression patterns of 11 randomly selected ZFP genes (at least one for each type) in normal fetal, adult and hypertrophic adult hearts, respectively, were determined using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis [17].
• Here the authors report a strategy for drug screening employing isogenic human cell lines in which the expression of the target protein is regulated by a gene-specific engineered zinc-finger protein (ZFP) transcription factor (TF) [18].

References