Altered methylation of specific DNA loci in the liver of Bhmt‐null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci

Lupu, Daniel S.; Orozco, Luz D.; Wang, Ying; Cullen, John M.; Pellegrini, Matteo; Zeisel, Steven H.

doi:10.1096/fj.201601169r

Cited by 16 publications

(18 citation statements)

References 54 publications

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“…One of the important functions of choline is to serve as a methyl-group donor used for the synthesis of Ado-Met (1). AdoMet concentrations are diminished, and S-adenosylhomocysteine (AdoHcy) concentrations are increased in animals consuming LC diets (33,34); the ratio of these 2 metabolites determines the rate of methylation reactions (35,36). Therefore, we assayed AdoMet and AdoHcy concentrations in AC and LC E17 brains.…”

Section: Choline-mediated Changes In Methylation Potential Regulate Ementioning

confidence: 99%

MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex

et al. 2018

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Choline availability modulates neurogenesis and cerebral cortex development through the regulation of neural progenitor cell (NPC) proliferative and differentiation capacity. In this study, we demonstrated that cortical NPC self‐renewal is controlled by choline via the expression of a microRNA (miR‐129‐5p), whose role in the developing brain has not been examined, and which, in turn, inhibits synthesis of the epidermal growth factor receptor (EGFR) protein. Specifically, we found that low choline (LC) availability led to the upregulation of miR‐129‐5p expression in cortical NPCs in vitro and in vivo, causing the downregulation of EGFR and thereby disrupting NPC self‐renewal and cortical neurogenesis. Furthermore, in response to LC availability, methylation potential (the S‐adenosylmethionine:S‐adenosylhomocysteine ratio) in the developing brain was reduced. Restoring methylation potential in LC cortical NPCs led to the re‐establishment of normal miR‐129‐5p expression. We concluded that inhibiting miR‐129‐5p function and restoring EGFR protein levels in vivo is sufficient to reverse LC‐induced defects in cortical NPC self‐renewal. For the first time, to our knowledge, we have identified the molecular links that explain how a change in the availability of the diet metabolite choline impacts the essential cellular processes underlying brain development.—Trujillo‐Gonzalez, I., Wang, Y., Friday, W. B., Vickers, K. C., Toth, C. L., Molina‐Torres, L., Surzenko, N., Zeisel, S. H. MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex. FASEB J. 33, 3601–3612 (2019). http://www.fasebj.org

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Section: Choline-mediated Changes In Methylation Potential Regulate Ementioning

confidence: 99%

MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex

et al. 2018

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“…While some oncogenes such as c-myc were hypomethylated in this low choline-diet rodent model, the promoter of some tumor suppressor genes such as p53, p16INK4a, PtprO, Cdh1, and Cx26 was hypermethylated [170,171,172]. In support of the role of betaine and choline in protecting against hepatocellular carcinoma, Lupu et al, [173] reported that, in a mouse model, the deletion of betaine-homocysteine methyltransferase gene, which is implicated in choline metabolism resulted in the spontaneous elevation of S-adenosylhomocysteine levels and development of preneoplastic foci in the liver.…”

Section: Micronutrients and Dna Methylation And Their Impact On Camentioning

confidence: 74%

Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome

2019

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DNA methylation is an epigenetic mechanism that is essential for regulating gene transcription. However, aberrant DNA methylation, which is a nearly universal finding in cancer, can result in disturbed gene expression. DNA methylation is modified by environmental factors such as diet that may modify cancer risk and tumor behavior. Abnormal DNA methylation has been observed in several cancers such as colon, stomach, cervical, prostate, and breast cancers. These alterations in DNA methylation may play a critical role in cancer development and progression. Dietary nutrient intake and bioactive food components are essential environmental factors that may influence DNA methylation either by directly inhibiting enzymes that catalyze DNA methylation or by changing the availability of substrates required for those enzymatic reactions such as the availability and utilization of methyl groups. In this review, we focused on nutrients that act as methyl donors or methylation co-factors and presented intriguing evidence for the role of these bioactive food components in altering DNA methylation patterns in cancer. Such a role is likely to have a mechanistic impact on the process of carcinogenesis and offer possible therapeutic potentials.

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“…The fourth gene in this region, ARSB , plays no apparent role in betaine metabolism, but does impact body size and craniofacial morphology through alternative mechanisms. However, variation in the nearby BHMT gene is associated with differential methylation of ARSB , which can modulate ARSB expression (Lupu et al. 2017).…”

Section: Resultsmentioning

confidence: 99%

Genomic Basis of Convergent Island Phenotypes in Boa Constrictors

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Adams

Schield

et al. 2019

Genome Biology and Evolution

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Convergent evolution is often documented in organisms inhabiting isolated environments with distinct ecological conditions and similar selective regimes. Several Central America islands harbor dwarf Boa populations that are characterized by distinct differences in growth, mass, and craniofacial morphology, which are linked to the shared arboreal and feast-famine ecology of these island populations. Using high-density RADseq data, we inferred three dwarf island populations with independent origins and demonstrate that selection, along with genetic drift, has produced both divergent and convergent molecular evolution across island populations. Leveraging whole-genome resequencing data for 20 individuals and a newly annotated Boa genome, we identify four genes with evidence of phenotypically relevant protein-coding variation that differentiate island and mainland populations. The known roles of these genes involved in body growth (PTPRS, DMGDH, and ARSB), circulating fat and cholesterol levels (MYLIP), and craniofacial development (DMGDH and ARSB) in mammals link patterns of molecular evolution with the unique phenotypes of these island forms. Our results provide an important genome-wide example for quantifying expectations of selection and convergence in closely related populations. We also find evidence at several genomic loci that selection may be a prominent force of evolutionary change—even for small island populations for which drift is predicted to dominate. Overall, while phenotypically convergent island populations show relatively few loci under strong selection, infrequent patterns of molecular convergence are still apparent and implicate genes with strong connections to convergent phenotypes.

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Altered methylation of specific DNA loci in the liver of Bhmt‐null mice results in repression of Iqgap2 and F2rl2 and is associated with development of preneoplastic foci

Cited by 16 publications

References 54 publications

MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex

MicroRNA‐129‐5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex

Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome

Genomic Basis of Convergent Island Phenotypes in Boa Constrictors

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