title: delta-Globin gene structure and expression in the K562 cell line.
abstract: The delta-globin gene produces the delta chain of Hb A2 which represents less than 3% of the hemoglobin (Hb) in normal individuals. The delta-globin gene is also expressed in the human erythroleukemia cell line K562. The expression of the delta-globin gene in this cell line is unexpected since K562 shows an embryonic-fetal globin gene expression pattern with no expression of the adult beta-globin gene. delta-Globin gene activation has been proposed as a potential therapeutic tool for the cure of delta-thalassemia (thal). In order to shed some light on the delta-globin gene activation in K562 the present study has: (1) determined the complete nucleotide sequence of the delta- and beta-globin genes; (2) assessed, by reverse transcription-polymerase chain reaction (RT-PCR), the relative delta- and beta-globin mRNA level; and (3) analyzed the exact level of the endogenous expression delta-globin gene by S1 mapping. No sequence variations were identified in the (delta- and beta-globin genes when compared to the normal sequences. delta-Globin mRNA represent more than 95% of the total delta + beta-mRNA content. The level of expression of the delta-globin gene is 12.3% (+/- 1.2) compared to the endogenous alpha-globin gene. These results indicate that the high expression of the delta-globin gene in K562 is most likely due to the transacting environment. Therefore, the presence and/or absence of specific transacting factors are able to specifically activate the human delta-globin gene. The level of expression of the delta-globin gene in this cell line suggests that it could be of relevance to identify the transacting factor(s) responsible for this selective activation in order to better understand the molecular mechanisms undergoing gene activation.
authors.affiliation: Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche (CNR), Selargius, Sardinia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Poddie
authors.forename: Maria F
authors.initials: MF
authors.lastname: Marongiu
authors.forename: Silvia Cigliuti
authors.initials: SC
authors.lastname: Ferrari
authors.forename: Susanna
authors.initials: S
authors.lastname: Porcu
authors.forename: Maria S
authors.initials: MS
authors.lastname: Ristaldi
mesh_terms: D005786:Gene Expression Regulation; D014644:Genetic Variation; D005914:Globins / Q000032:analysis / Q000235:genetics*; D006443:Hemoglobin A2 / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D015533:Transcriptional Activation
chemical_list: D012333:RNA, Messenger; D005914:Globins; D006443:Hemoglobin A2