NAD Modulates DNA Methylation and Cell Differentiation
Nutritional intake impacts the human epigenome by directing epigenetic pathways in normal cell development via as yet unknown molecular mechanisms. Consequently, imbalance in the nutritional intake is able to dysregulate the epigenetic profile and drive cells towards malignant transformation. Here w...
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MDPI AG
2021
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oai:doaj.org-article:95f6f216f4354e839427510a4d5e52e52021-11-25T17:10:05ZNAD Modulates DNA Methylation and Cell Differentiation10.3390/cells101129862073-4409https://doaj.org/article/95f6f216f4354e839427510a4d5e52e52021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/2986https://doaj.org/toc/2073-4409Nutritional intake impacts the human epigenome by directing epigenetic pathways in normal cell development via as yet unknown molecular mechanisms. Consequently, imbalance in the nutritional intake is able to dysregulate the epigenetic profile and drive cells towards malignant transformation. Here we present a novel epigenetic effect of the essential nutrient, NAD. We demonstrate that impairment of DNMT1 enzymatic activity by NAD-promoted ADP-ribosylation leads to demethylation and transcriptional activation of the <i>CEBPA</i> gene, suggesting the existence of an unknown NAD-controlled region within the locus. In addition to the molecular events, NAD- treated cells exhibit significant morphological and phenotypical changes that correspond to myeloid differentiation. Collectively, these results delineate a novel role for NAD in cell differentiation, and indicate novel nutri-epigenetic strategies to regulate and control gene expression in human cells.Simone UmmarinoClinton HausmanGiulia GaggiLucrezia RinaldiMahmoud A. BassalYanzhou ZhangAndy Joe SeelamIkei S. KobayashiMarta BorchielliniAlexander K. EbralidzeBarbara GhinassiBon Q. TrinhSusumu S. KobayashiAnnalisa Di RuscioMDPI AGarticleepigeneticsDNA methylationNADgene regulationBiology (General)QH301-705.5ENCells, Vol 10, Iss 2986, p 2986 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
epigenetics DNA methylation NAD gene regulation Biology (General) QH301-705.5 |
| spellingShingle |
epigenetics DNA methylation NAD gene regulation Biology (General) QH301-705.5 Simone Ummarino Clinton Hausman Giulia Gaggi Lucrezia Rinaldi Mahmoud A. Bassal Yanzhou Zhang Andy Joe Seelam Ikei S. Kobayashi Marta Borchiellini Alexander K. Ebralidze Barbara Ghinassi Bon Q. Trinh Susumu S. Kobayashi Annalisa Di Ruscio NAD Modulates DNA Methylation and Cell Differentiation |
| description |
Nutritional intake impacts the human epigenome by directing epigenetic pathways in normal cell development via as yet unknown molecular mechanisms. Consequently, imbalance in the nutritional intake is able to dysregulate the epigenetic profile and drive cells towards malignant transformation. Here we present a novel epigenetic effect of the essential nutrient, NAD. We demonstrate that impairment of DNMT1 enzymatic activity by NAD-promoted ADP-ribosylation leads to demethylation and transcriptional activation of the <i>CEBPA</i> gene, suggesting the existence of an unknown NAD-controlled region within the locus. In addition to the molecular events, NAD- treated cells exhibit significant morphological and phenotypical changes that correspond to myeloid differentiation. Collectively, these results delineate a novel role for NAD in cell differentiation, and indicate novel nutri-epigenetic strategies to regulate and control gene expression in human cells. |
| format |
article |
| author |
Simone Ummarino Clinton Hausman Giulia Gaggi Lucrezia Rinaldi Mahmoud A. Bassal Yanzhou Zhang Andy Joe Seelam Ikei S. Kobayashi Marta Borchiellini Alexander K. Ebralidze Barbara Ghinassi Bon Q. Trinh Susumu S. Kobayashi Annalisa Di Ruscio |
| author_facet |
Simone Ummarino Clinton Hausman Giulia Gaggi Lucrezia Rinaldi Mahmoud A. Bassal Yanzhou Zhang Andy Joe Seelam Ikei S. Kobayashi Marta Borchiellini Alexander K. Ebralidze Barbara Ghinassi Bon Q. Trinh Susumu S. Kobayashi Annalisa Di Ruscio |
| author_sort |
Simone Ummarino |
| title |
NAD Modulates DNA Methylation and Cell Differentiation |
| title_short |
NAD Modulates DNA Methylation and Cell Differentiation |
| title_full |
NAD Modulates DNA Methylation and Cell Differentiation |
| title_fullStr |
NAD Modulates DNA Methylation and Cell Differentiation |
| title_full_unstemmed |
NAD Modulates DNA Methylation and Cell Differentiation |
| title_sort |
nad modulates dna methylation and cell differentiation |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/95f6f216f4354e839427510a4d5e52e5 |
| work_keys_str_mv |
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1718412666492420096 |