A model for silencing the erythropoietin gene by methylation.

Methylation of CpGs in a cis element upstream of the GATA box prevents the binding of a trans-acting protein, impairing transcriptional activation. The sequence-specific binding activity may contain aryl hydrocarbon nuclear translocator (ARNT). Methylation of high-density CpGs in the erythropoietin 5′-UTR recruits a methyl-CpG–binding protein (MeCP) that represses transcription by engaging corepressors (Co-R), histone deacetylases, or both.