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Expression and Developmental Control of the Human α‐Globin Gene Cluster
Author(s) -
LIEBHABER STEPHEN A.,
RUSSELL J. ERIC
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10462.x
Subject(s) - gene silencing , globin , biology , locus control region , microbiology and biotechnology , gene , gene cluster , gene expression , untranslated region , regulation of gene expression , genetics , locus (genetics) , messenger rna , promoter
A bstract : The human α‐globin gene cluster contains three functional genes ζ, α2 and α1. The ζ‐globin gene is expressed exclusively in the primitive erythroblasts of the embryonic yolk sac and is selectively silenced during the transition from primitive to definitive erythropoesis. The two α‐globin genes are expressed through development; they are expressed at equivalent levels in embryonic cells at a 2.6: 1 ratio of α2 : α1 in fetal and adult cells. The dominant contribution of the α2‐globin locus to overall expression of adult α‐globin is reflected in the more severe phenotype resulting from mutations that affect this locus. Developmental silencing of the ζ‐globin gene reflects both transcriptional and posttranscriptional mechanisms. Transcriptional silencing is mediated by an interaction between the ζ‐globin gene promoter and a silencer located in the 3′ flanking region. This transcriptional silencing is only partial, and residual levels of ζ‐globin mRNA are subject to subsequent degredation. This instability of ζ‐globin mRNA relative to that of α‐globin mRNA reflects differences in their respective 3′UTR segments; the ζ‐globin mRNA 3′UTR has a lower affinity for a sequence‐specific mRNP stability complex which assembles at this site. The α‐globin mRNA assembles this complex at a higher efficiency and mutations which interfere with 3′UTR function result in corresponding loss of α‐globin gene expression. These data outline a developmental pathway for the α‐globin gene cluster which reflects transcriptional and posttranscriptional controls.