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ZNF536 is a recently identified zinc-finger protein that is expressed primarily in the developing nervous system and the cerebral cortex, hippocampus, and hypothalamus. ZNF536 possess ten zinc fingers and interacts with CtBP1, a corepressor for gene transcription. It is most closely related to transcriptional repressor ZNF219. Overexpression of ZNF536 in embryonic stem cells dramatically reduced the mRNA levels of neuronal marker genes such as Pax6, MAP2, and beta-tubulin III following retinoic acid (RA)-induced differentiation, while depletion of ZNF536 via RNAi resulted in elevated mRNA levels of these genes, indicating its role in inhibiting neuronal cell differentiation. Overexpression of RA receptor a rescues the inhibitory role of ZNF536, suggesting that ZNF536 might inhibit RA response element-mediated transcriptional activity.