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Laura J. Norton, Alister P.W. Funnell (2017)
KLF1 directly activates expression of the novel fetal globin repressor ZBTB7A/LRF in erythroid cells
Blood Advances 1:685-692

(Translated by Wassal Alhammad)

Significance

Hemoglobin (Hb) is a vital protein for human beings (Fig. 1). It carries the oxygen to the different tissues and organs. This hemoglobin comes in three major types and one them is expressed predominantly in each period; Embryonic Hb, which is produced in the early embryonic period, Fetal Hb (HbF) which is produced late during pregnancy when embryonic Hb starts to switch off, and finally Adult Hb, which is expressed just before fetus are delivered. Genetics disorders such as sickle cell anemia and β-thalassemia are examples of diseases that affect only the adult hemoglobin. Therefore, understanding the mechanism of Hb switching is very important to reverse the switching and treat these diseases.

The significance of this study comes from its aim to uncover parts of the molecular basis of hemoglobin switching. This study build upon previous finding that Kruppel-like transcription factor 1 (KLF1) is a central protein in many processes related to hemoglobin metabolism and red blood cell development. It was shown that KLF1 regulates the expression of many repressor proteins such as BCL11A. ZBTB7A is another repressor protein that works similar to BCL11A in repressing the production of HbF. Unlike BCL11A, not much is known about the regulation of ZBTB7A expression. Understanding such mechanism of regulation is important as an alternative pathway for treatment strategies of Sickle cell anemia and β-thalassemia

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Fig. 1: Structure of Human Hemoglobin protien (Hb): Hemoglobin is a protien composed of four subunit, polypeptide chain (red and blue-colored chains). two alpha chains (red chains) and two beta chains (blue chains). Each chain contains a heme group, which a cyclic organic compound to hold iron (Fe) in (light gray dots), in the center (dark gray oval). The heme group is responsible for carrying oxygen from to the tissue. Image taken from
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