ENETIC NUTRITION: EPIGENETICS, GENOMICS, & PROTEOMICS 2002...

GENETIC NUTRITION: EPIGENETICS, GENOMICS, & PROTEOMICS 2002: SILENCING ìBADî AND ACTIVATING ìGOODî DNA, mRNA TRANSCRIPTS, AND THEIR PROTEINS, BY TARGETED CHROMATIN METHYLATION AND DEMETHYLATION.

Victor D. Herbert, MD, JD, MACP. Mount Sinai-NYU Health System & Bronx V.A. Medical Center, Bronx, NY, 10468 United States.

In our chapter ìInhibition of Some Cancers and Promotion of Others by Folic Acid, Vitamin B₁₂, and Their Antagonistsî in Nutritional Factors in Induction and Maintenance of Malignancy (Butterworth CE Jr, Hutchinson ML, Eds. NY: Academic Press, 1983:273-87), we wrote, ìI should like to suggest the hypothesis that deficiency of folate or vitamin B₁₂, or any other cause of failure to methylate DNA and/or RNA, can activate malignancy by hypomethylation of oncogenes, and that methylating oncogenes can inhibit malignancy by making them dormant.î The NIH Aug 6-8, 2001, Trans HHS Workshop, ìDiet, DNA Methylation Processes, and Healthî (In press, J Nutr), presented new genomic research confirming that any DNA, RNA, or proteome allele can be epigenetically silenced by methylation or activated by demethylation. Methylation can be via transcription-repressing protein complexes (Dnmts, HDACs, etc). Hypermethylation can suppress oncogenes, or, conversely, promote cancers by suppressing tumor suppressor genes, RNAs, and proteins which suppress angiogenesis, metastasis, and DNA repair genes. A Wolffeís group reported one can epigenetically silence by targeted methylation of its unique single nucleotide polymorphisms (SNPs), with tailored zinc finger ìbulletsî, solely the unique gene variant chromatin target one wishes, with eventual prevention and cure of not only cancers, but all disorders associated with inherited or acquired gene variant chromatin. Thus, the future of genetic nutrition may be largely identifying all bad and good SNPs, isolating them from body fluids using high-throughput genetic analysis instrumentation (C M Henry. Pharmacogenomics. Chem & Eng News, 2001; 79 (33): 37-42), then silencing the bad and activating the good.

CV#841A. Herbert V. Genetic Nutrition: Epigenetics, Genomics, & Proteomics 2002: Silencing ìBadî And Activating ìGoodî DNA, mRNA Transcripts, And Their Proteins, By Targeted Chromatin Methylation And Demethylation. AJCN, in press 2002. (Submitted to the First Annual Nutrition Week, February 23-27, San Diego Convention Center, CA).