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Zinc-fingers and homeobox (ZHX) proteins are transcription factors that interact with the activation domain of the A subunit of nuclear factor-Y (NF-YA). ZHX1-3 are ubiquitously expressed proteins expressed in various tissues. They act as transcriptional repressors and localize to the nucleus. The ZHX proteins contain two Cys(2)-His(2)-type zinc-finger motifs and five homeodomains (HDs). These domains allow the ZHX proteins to form homodimers, but they can also form heterodimers with each other. However, this dimerization is not required for repressor activity. Hypermethylation-mediated silencing of ZHX2 is an epigenetic event involved in hepatocellular carcinoma (HCC).
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