Disease relevance of ZNF74

• We now report that one of them, ZNF74 gene, is hemizygously deleted in 23 out of 24 DiGeorge syndrome patients tested [1].

High impact information on ZNF74

• Hamster-human somatic hybrid cell lines from a patient with der(22) syndrome and a patient with VCFS showed that the breakpoints occurred in an interval containing low-copy repeats, distal to RANBP1 and proximal to ZNF74 [2].
• Furthermore, we demonstrate that KAP-1 but not TIF1alpha interacts with the KRAB multifinger ZNF74 in the nuclear matrix [3].
• Oligomerization of transcriptional intermediary factor 1 regulators and interaction with ZNF74 nuclear matrix protein revealed by bioluminescence resonance energy transfer in living cells [3].
• We now report on the multifunctionality of the zinc finger domain of ZNF74 [4].
• By far-Western analysis and coimmunoprecipitation studies, we demonstrate that ZNF74 interacts, via its zinc finger domain, with the hyperphosphorylated largest subunit of RNA polymerase II (pol IIo) but not with the hypophosphorylated form [4].

Biological context of ZNF74

• The restricted binding to these homopolymers and not to poly(A) and poly(C) suggested that ZNF74 displays RNA sequence preferences [5].
• The importance of the phosphorylation in this interaction is supported by the observation that phosphatase treatment inhibits ZNF74 binding [4].
• The RNA binding properties of this protein and its tight association with the nuclear matrix, a subnuclear compartment involved in DNA replication as well as RNA synthesis and processing, suggest a role for ZNF74 in RNA metabolism [5].
• Association of ZNF74 gene genotypes with age-at-onset of schizophrenia [6].
• Thus, the restricted expression of ZNF74 in structures affected in DGS suggests a role for this putative regulator of gene expression in aspects of the DGS phenotype [7].

Anatomical context of ZNF74

• Subcellular and in situ sequential fractionations further showed that ZNF74 is associated with the nuclear matrix [5].
• ZNF74, a gene deleted in DiGeorge syndrome, is expressed in human neural crest-derived tissues and foregut endoderm epithelia [7].
• Interestingly, ZNF74 expression was detected in the wall of the pulmonary artery and aorta and in the aortic valve, which are populated by neural crest-derived cells [7].
• In situ hybridization on Carnegie Stage 18 embryos revealed that ZNF74 expression is limited to specific neural crest-derived tissues and neuroepithelium of the spinal cord as well as to foregut endoderm epithelia (esophagus and respiratory tract) [7].

Other interactions of ZNF74

• The interaction of ZNF74 with KAP-1 did not prevent KAP-1 homomerization indicating that the oligomers most likely represent the transcriptionally active species [3].

Analytical, diagnostic and therapeutic context of ZNF74

• Immunofluorescence studies on transfected cells revealed ZNF74 nuclear localization [5].

References