Investigating the Role of Methylation in Silencing of VDR Gene Expression in Normal Cells during Hematopoiesis and in Their Leukemic Counterparts

Nowak, Urszula; Janik, Sylwia; Marchwicka, Aleksandra; Łaszkiewicz, Agnieszka; Jakuszak, Agnieszka; Cebrat, Małgorzata; Marcinkowska, Ewa

doi:10.3390/cells9091991

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Investigating the Role of Methylation in Silencing of VDR Gene Expression in Normal Cells during Hematopoiesis and in Their Leukemic Counterparts

Urszula Nowak

¹,

Sylwia Janik

²,

Aleksandra Marchwicka

¹,

Agnieszka Łaszkiewicz

²,

Agnieszka Jakuszak

¹,

Małgorzata Cebrat

^2,* and

Ewa Marcinkowska

^1,*

Laboratory of Protein Biochemistry, Faculty of Biotechnology, University of Wrocław, Joliot-Curie 14a, 50-383 Wrocław, Poland

Laboratory of Molecular and Cellular Immunology, Department of Tumor Immunology, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Weigla 12, 53-114 Wrocław, Poland

Authors to whom correspondence should be addressed.

Cells 2020, 9(9), 1991; https://doi.org/10.3390/cells9091991

Received: 4 June 2020 / Revised: 19 August 2020 / Accepted: 26 August 2020 / Published: 29 August 2020

(This article belongs to the Special Issue Nuclear Receptor Signaling and Cancer)

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Abstract

(1) Background: Vitamin D receptor (VDR) is present in multiple types of blood cells, and its ligand, 1,25-dihydroxyvitamin D (1,25D), is important for the proper functioning of the immune system. Activity of VDR is higher in hematopoietic stem and progenitor cells than in fully differentiated blood cells of mice and humans. In some human acute myeloid leukemia (AML) blasts, the expression of the VDR gene is also high. The mechanism of silencing the VDR gene expression during differentiation of blood cells has been addressed in this work. (2) Methods: The cells have been obtained using fluorescence activated sorting from murine tissues and from human umbilical cord blood (UCB). Then, the expression of the VDR gene and transcriptional activity of the VDR protein has been tested in real-time polymerase chain reaction (PCR). Eventually, the methylation of VDR promoter regions was tested using bisulfite sequencing. (3) Results: The CpG islands in VDR promoters were not methylated in the cells studied both in mice and in humans. The use of hypomethylating agents had no effect toward expression of human VDR transcripts, but it increased expression of the VDR-target gene, CYP24A1. (4) Conclusions: The expression of the VDR gene and transcriptional activity of the VDR protein varies at successive stages of hematopoietic differentiation in humans and mice, and in blasts from AML patients. The experiments presented in this case indicate that methylation of the promoter region of the VDR gene is not the major mechanism responsible for these differences. View Full-Text

Keywords: blood cells; vitamin D receptor; gene expression; hematopoietic stem cells; hematopoietic progenitor cells; differentiation; methylation; leukemia

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Nowak, U.; Janik, S.; Marchwicka, A.; Łaszkiewicz, A.; Jakuszak, A.; Cebrat, M.; Marcinkowska, E. Investigating the Role of Methylation in Silencing of VDR Gene Expression in Normal Cells during Hematopoiesis and in Their Leukemic Counterparts. Cells 2020, 9, 1991. https://doi.org/10.3390/cells9091991

AMA Style

Nowak U, Janik S, Marchwicka A, Łaszkiewicz A, Jakuszak A, Cebrat M, Marcinkowska E. Investigating the Role of Methylation in Silencing of VDR Gene Expression in Normal Cells during Hematopoiesis and in Their Leukemic Counterparts. Cells. 2020; 9(9):1991. https://doi.org/10.3390/cells9091991

Chicago/Turabian Style

Nowak, Urszula, Sylwia Janik, Aleksandra Marchwicka, Agnieszka Łaszkiewicz, Agnieszka Jakuszak, Małgorzata Cebrat, and Ewa Marcinkowska. 2020. "Investigating the Role of Methylation in Silencing of VDR Gene Expression in Normal Cells during Hematopoiesis and in Their Leukemic Counterparts" Cells 9, no. 9: 1991. https://doi.org/10.3390/cells9091991

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Investigating the Role of Methylation in Silencing of VDR Gene Expression in Normal Cells during Hematopoiesis and in Their Leukemic Counterparts

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