title: beta-Minor globin gene expression is preferentially reduced in EKLF Knock-Out mice.
abstract: The CACCC box is duplicated in the beta-globin gene promoter of humans and other mammals. While the function of the proximal element as a binding site for EKLF has already been well established, the role of the distal element remains unclear. Mice present two adult beta-globin genes, beta-major and beta-minor, bearing a single CACCC box, the consensus sequence of which is identical to that of the proximal or distal human element, respectively. In the present study we analyzed the mRNA expression of beta-minor and beta-major in EKLF Knock-Out (KO) mice in comparison to wild-type (wt) littermates. The murine early fetal liver up to day 13/14 post coitum (pc) expresses mainly beta-minor globin chains. Nevertheless, expression of the beta-minor globin gene in EKLF KO mice has not been assessed to date. We provide evidence that expression of the beta-minor globin gene is dependent upon EKLF and is more affected by EKLF deprivation than the beta-major gene. The results obtained support a general role of EKLF in beta-globin gene activation and are in agreement with models involving an advantage of the LCR proximal respect to distal gene.
authors.affiliation: Istituto di Neurogenetica e Neurofarmacologia (INN) del Consiglio Nazionale delle Ricerche (CNR), Selargius (CA), Cagliari, Sardinia, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Porcu
authors.forename: Daniela
authors.initials: D
authors.lastname: Poddie
authors.forename: Marco
authors.initials: M
authors.lastname: Melis
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Maria Serafina
authors.initials: MS
authors.lastname: Ristaldi
mesh_terms: D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D020033:Protein Isoforms / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D020033:Protein Isoforms; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor; D012313:RNA; D005914:Globins