δ-Globin Gene Structure and Expression in the K562 Cell Line

• Published in: Hemoglobin Vol. 27; no. 4; pp. 219 - 228
• Main Authors: Poddie, Daniela, Marongiu, Maria F., Ferrari, Silvia Cigliuti, Porcu, Susanna, Ristaldi, Maria S.
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.01.2003; Taylor & Francis
• Subjects: Gene expression and structure; Gene Expression Regulation; Genetic Variation; Globins - analysis; Globins - genetics; Hemoglobin A2 - genetics; Humans; K562 cell line; K562 Cells; RNA, Messenger - analysis; Sequence Analysis, DNA; Transcriptional Activation; δ-Globin gene
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1081/HEM-120026046

The δ-globin gene produces the δ chain of Hb A2 which represents less than 3% of the hemoglobin (Hb) in normal individuals. The δ-globin gene is also expressed in the human erythroleukemia cell line K562. The expression of the δ-globin gene in this cell line is unexpected since K562 shows an embryonic-fetal globin gene expression pattern with no expression of the adult β-globin gene. δ-Globin gene activation has been proposed as a potential therapeutic tool for the cure of δ-thalassemia (thal). In order to shed some light on the δ-globin gene activation in K562 the present study has: (1) determined the complete nucleotide sequence of the δ- and β-globin genes; (2) assessed, by reverse transcription-polymerase chain reaction (RT-PCR), the relative δ- and β-globin mRNA level; and (3) analyzed the exact level of the endogenous expression δ-globin gene by S1 mapping. No sequence variations were identified in the δ- and β-globin genes when compared to the normal sequences. δ-Globin mRNA represent more than 95% of the total δ + β-mRNA content. The level of expression of the δ-globin gene is 12.3% (±1.2) compared to the endogenous α-globin gene. These results indicate that the high expression of the δ-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 δ-globin gene. The level of expression of the δ-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.