The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders

The EZH2 gene is a homolog of the Drosophila Polycomb group (PcG) gene enha ncer of zest, a crucial regulator of homeotic gene expression. Several line s of evidence suggest a critical role for the EZH2 protein during normal an d perturbed development of the haematopoietic and central nervous systems. Indeed, the EZH2 protein has been shown to associate with the Vav proto-onc oprotein and with the XNP protein, the product of a mental retardation gene . The EZH2 gene was previously reported to be located on chromosome 21q22 a nd was proposed as a candidate gene for some characteristics of the Down sy ndrome phenotype. We report here the genomic structure and fine mapping of the EZH2 gene. We demonstrate that the functional gene actually maps to chr omosome 7q35 and that the sequence previously isolated from a chromosome 21 cosmid corresponds to a pseudogene. Finally, the nature of the EZH2 protei n and its mapping to the critical region for malignant myeloid disorders le ad us to propose the EZH2 gene is involved in the pathogenesis of 7q35-q36 aberrations in myeloid leukaemia.