Cytosine methylation in miR-153 gene promoters increases the expression of holocarboxylase synthetase,thereby increasing the abundance of histone H4 biotinylation marks in HEK-293 human kidney cells |
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| Authors: | Baolong Bao Rocio Rodriguez-Melendez Janos Zempleni |
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| Institution: | 1. Department of Nutrition and Health Sciences, University of Nebraska at Lincoln, Lincoln, NE, 68583, USA;2. Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai 201 306, China;1. Department of Agronomy and Plant Genetics, University of Minnesota, 1991 Buford Circle, St. Paul, MN 55108, USA;2. USDA-ARS-RRVARC-NCSL, Cereal Crops Research Unit, Hard Spring and Durum Wheat Quality Laboratory, NDSU Dept. 7640, PO Box 6050, Fargo, ND 58102-6050, USA;3. The Land Institute, 2440 E Water Well Road, Salina, KS 67401, USA;1. Department of Biochemistry and Cell Biology, State University of New York, Stony Brook, NY, 11794-5215, USA;2. Department of Biosciences, COMSATS Institute of Information Technology Islamabad, Park Road, Islamabad, 44000, Pakistan;1. Department of Anatomical Pathology, St Vincent''s Hospital Fitzroy, Australia;2. Department of Pathology, The University of Melbourne, Australia;3. Department of Surgery, St Vincent''s Hospital, Fitzroy, Australia;4. Department of Oncology, St Vincent''s Hospital, Fitzroy, Australia;5. Department of Respiratory Medicine, St Vincent''s Hospital, Fitzroy, Vic, Australia;1. Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México and Instituto Nacional de Pediatría, México City, México;2. Lab. Nutrición Experimental, Instituto Nacional de Pediatría, México City, México |
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| Abstract: | Holocarboxylase synthetase (HCS) plays an essential role in catalyzing the biotinylation of carboxylases and histones. Biotinylated carboxylases are important for the metabolism of glucose, lipids and leucine; biotinylation of histones plays important roles in gene regulation and genome stability. Recently, we reported that HCS activity is partly regulated by subcellular translocation events and by miR-539. Here we tested the hypothesis that the HCS 3′-untranslated region (3′-UTR) contains binding sites for miR other than miR-539. A binding site for miR-153 was predicted to reside in the HCS 3′-UTR by using in silico analyses. When miR-153 site was overexpressed in transgenic HEK-293 human embryonic kidney cells, the abundance of HCS mRNA decreased by 77% compared with controls. In silico analyses also predicted three putative cytosine methylation sites in two miR-153 genes; the existence of these sites was confirmed by methylation-sensitive polymerase chain reaction. When cytosines were demethylated by treatment with 5-aza-2′-deoxycytidine, the abundance of miR-153 increased by more than 25 times compared with untreated controls, and this increase coincided with low levels of HCS and histone biotinylation. Together, this study provides novel insights into the mechanisms of novel epigenetic synergies among folate-dependent methylation events, miR and histone biotinylation. |
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