Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Hemoglobin and globin genes are important models for studying protein and gene structure, function and regulation. We reviewed the main aspects of regulation of human alpha-globin synthesis, encoded by two adjacent genes (alpha 2 and alpha 1) clustered on chromosome 16. Their expression is controlled mainly by a regulatory element located 40 kb upstream on the same chromosome, the alpha-major regulatory element, whose activity is restricted to a core fragment of 350 bp, within which several regulatory protein binding sites have been found. Natural deletions involving alpha-major regulatory element constitute a particular category of alpha-thalassemia determinants in which the alpha-globin genes are physically intact but functionally inactive.7410451053Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [02/13801-7, 03/07412-0]CNPq [475481/2006-2]