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Alternative titles; symbolsKIAA0390HGNC Approved Gene Symbol: ZNF536Cytogenetic location: 19q12 Genomic coordinates (GRCh38): 19:30,224,235-30,713,585 (from ...

Alternative titles; symbols

  • KIAA0390

HGNC Approved Gene Symbol: ZNF536

Cytogenetic location: 19q12 Genomic coordinates (GRCh38): 19:30,224,235-30,713,585 (from NCBI)

▼ Description
ZNF536 is a brain-specific transcriptional repressor that inhibits retinoic acid (RA)-driven neuron differentiation (Qin et al., 2009).

▼ Cloning and Expression
By analyzing proteins interacting with the transcriptional repressor Ctbp1 (602618) in mouse brain, Qin et al. (2009) identified Znf536 and human ZNF536. The 1,302-amino acid ZNF536 protein contains 10 Kruppel-like C2H2 zinc finger domains and a CTBP-binding motif; it shares 88% amino acid identity with the mouse protein and at least 86% amino acid similarity to orthologous genes in rat, dog, chicken, and zebrafish. Northern blot analysis showed strong Znf536 expression in adult mouse brain, with weaker expression in heart and testis and no expression in liver, spleen, lung, kidney, or stomach. In situ hybridization experiments in E9.5 and E10.5 mouse embryos showed Znf536 expression in the central nervous system, dorsal root ganglia, eye vesicles, forelimb buds, forebrain, midbrain, hindbrain neural folds, telencephalic vesicles, and spinal cord. RT-PCR demonstrated that Znf536 was expressed in rat cerebral cortex, hippocampus, thalamus, and corpus striatum. Immunohistochemical staining showed Znf536 expression in mouse brain cerebral cortex, hippocampus, and hypothalamus. Znf536 staining overlapped with that of neuronal marker beta-3-tubulin (TUBB3; 602661) but not glial cell marker GFAP (137780), suggesting that Znf536 is expressed in neurons but not glia. Fluorescence staining showed that Znf536 localized to the nucleus of neurons.

▼ Gene Function
P19 mouse embryonic carcinoma cells differentiate into neurons when exposed to retinoic acid (RA). Using RT-PCR, Qin et al. (2009) showed that Znf536 and TUBB3 increased in P19 cells in response to RA stimulus. Znf536 levels remained high in differentiated cells after the suspension period, whereas TUBB3 levels decreased. Coimmunostaining showed that cells with lower levels of TUBB3 had higher levels of Znf536. Ectopic expression of wildtype human ZNF536 in P19 cells resulted in a reduction of neuron-like TUBB3-positive cells; expression of a CTBP-binding-defective ZNF536 or depletion of ZNF536 led to an increase in neuron-like cells. Overexpression of ZNF536 led to significantly inhibited RA-induced reporter activity in luciferase reporter experiments. This inhibition was not observed for mutant ZNF536 or when ZNF536 was silenced. EMSA analysis in P19 cells showed increased binding of ZNF536 to RA response elements (RAREs) when ZNF536 was overexpressed. ChIP analysis showed that both RA receptor (RAR)-alpha (180240) and ZNF536 bind to RAREs. Overexpression of both RAR-alpha and ZNF536 in 293T cells demonstrated that ZNF536 blocks RAR-alpha from binding to RAREs. RA induced RAR-alpha as well as RAR-alpha-dependent RARE reporter expression in mock- or mutant ZNF536-transfected cells, but not in the presence of wildtype ZNF536. Overexpression of RAR-alpha rescued the inhibitory effect of ZNF536 on RA stimulation. Qin et al. (2009) concluded that ZNF536 inhibits neuronal cell differentiation through RAR-alpha.

▼ Mapping
Gross (2018) mapped the ZNF536 gene to chromosome 19q12 based on an alignment of the ZNF536 sequence (GenBank BC132720) with the genomic sequence (GRCh38).

Tags: 19q12