Poster abstracts
Poster number 154 submitted by Anita Dhara
The role of pumilio homolog 1 (PUM1) in human hemoglobin switching and erythroid differentiation
Anita R. Dhara, (Department of Biological, Geological, and Environmental Sciences, Center for Gene Regulation in Health and Disease, Cleveland State University, OH-44115), Dr. Mahesh Ramamoorthy and (Department of Biological, Geological, and Environmental Sciences, Center for Gene Regulation in Health and Disease, Cleveland State University, OH-44115), Dr. Merlin Nithya Gnanapragasam (Department of Biological, Geological, and Environmental Sciences, Center for Gene Regulation in Health and Disease, Cleveland State University, OH-44115)
Abstract:
The conversion from fetal to adult hemoglobin occurs around birth, accompanied by a change in an expression level from γ-globin to the β-globin chain. Patients with high fetal hemoglobin levels (HbF) have a milder clinical manifestation of β-hemoglobinopathy, such as sickle cell anemia and β-thalassemia. Therefore, γ-globin (β-type of globin gene) provides a promising therapeutic option for replacing mutated or absent β-globin, thereby increasing fetal hemoglobin levels. However, in contrast to transcriptional and epigenetic control, post-transcriptional regulation of β-globin switching is poorly known, with few physiological and clinical studies. We have shown that PUM1, an RNA-binding protein, is a novel direct candidate for Erythroid Krüppel-like factor (EKLF), a master and transcriptional regulator of erythropoiesis. PUM1 binds to the fetal γ-globin mRNA and decreases γ-globin protein levels, demonstrating post-transcriptional regulation of fetal γ-globin. Similar results were observed with human primary CD34+ erythroid cells. Furthermore, we showed that PUM1 knockdown does not affect the progression of terminal erythroid differentiation. Our unpublished data for the PUM1 knockout showed similar results for γ-globin protein levels, corroborating our previous results. PUM1 knockout does not impair but rather augments human terminal erythroid differentiation. We will further characterize the PUM1 knockout cells to check any dose-dependent effects on erythroid terminal differentiation. Also, we will be investigating the impact of two putative binding sites at the 3’-UTR of HBG1 fetal γ-globin mRNA in regulating fetal hemoglobin profile.
References:
Elagooz R, Dhara AR, et al., Blood Advances, 2022 (Online ahead of print)
Keywords: Pumilio homolog 1 (PUM1), Hemoglobin switching, Erythroid terminal differentiation