Our recent experiments have revealed a new exon, 1g, regulated from the promoter of exon 1a. at early stages of their differentiation ATRA, but not 1,25D, upregulates the expression of expression in response to ATRA, depending on the AML cell line examined [12,13]. Since beneficial effects of 1,25D and ATRA combination treatment in anticancer therapy have been reported and their wider use postulated [14], the effects of such combination towards normal cells should be addressed. Hematopoiesis seems to be the most relevant process which might be influenced by ATRA and 1,25D. The roles of vitamin A and its most active metabolites during hematopoiesis have been extensively studied and are well appreciated [15]. The actions of RA are multiple, and they start as early as in embryonal yolk sac and aorta-gonad-mesonephros, where RA causes the appearance of hematopoietic progenitors from the hemogenic endothelium [16]. In adult hematopoiesis, RA is important for granulopoiesis, and it controls differentiation of B and T lymphocytes [15]. However, it should be remembered that, due to difficulties in the use of human models of hematopoiesis, mice models have often been used in the experiments [15]. The role of 1 1,25D in hematopoiesis is less well documented than that of ATRA; moreover, some STA-21 of the data come from zebrafish models. It should be remembered that, in contrast to humans and mice, there are two forms of VDR in zebrafish [17]. However, the available data show that the correct levels of 1,25D are necessary to maintain hematopoietic stem and progenitor cells (HSPCs) [18]. It was also shown that in human hematopoietic stem cells (HSCs) exposed to physiological concentrations of 1 1,25D, markers of monocytic differentiation are induced [19]. The gene encoding human VDR is located on chromosome 12. This gene is composed of 14 exons, and translation of VDR protein starts from the exon 2. Region 5 of human gene is very complex, and is composed of the seven exons 1aCg. These exons, together with corresponding promoter regions, are alternatively used for transcription in different tissues. Transcripts starting from exon 1a and from exon 1d are regulated by the common promoter upstream to exon 1a, and the exons 1f and 1c have separate upstream promoters [20]. Our recent experiments have revealed a new exon, 1g, regulated from the promoter of exon 1a. Exon 1g is used in transcripts present in AML cells [13]. Multiple publications confirm that expression in humans is regulated in response to ATRA [12,21,22,23], while there are conflicting reports concerning regulation of human by 1,25D [13,24,25,26]. The murine gene is located on chromosome 15, and its composition is less complex than in humans. In the 5 STA-21 UTR region of gene, exons 1 and 2 STA-21 were identified, which Rabbit Polyclonal to CPN2 show strong homology to human 1a and 1c, respectively [27]. Although exon 1d is well conserved (1d-like), transcripts containing this exon have not been reported in mice. The sequence similarity of the exons 1f and 1b is low between man and mice. Translation of mouse VDR protein starts from exon 3 [28]. It has been shown that transcription of is upregulated in response to 1 1,25D in murine osteoblasts [29,30]. This is why we decided to examine the effects of the 1,25D and ATRA combination on gene expression in blood cells STA-21 at various steps of their development..
Our recent experiments have revealed a new exon, 1g, regulated from the promoter of exon 1a
