Niacin status impacts chromatin structure.
Niacin is required to form NAD and NADP, which are involved in many essential redox reactions in cellular metabolism. In addition, NAD(+) acts as a substrate for a variety of ADP-ribosylation reactions, including poly- and mono-ADP-ribosylation of proteins, formation of cyclic ADP-ribose, and the generation of O-acetyl-ADP-ribose in deacetylation reactions. These nonredox reactions are critical in the regulation of cellular metabolism, and they are sensitive to dietary niacin status. There are 4 known mechanisms by which ADP-ribosylation reactions directly regulate chromatin structure. These include the covalent modification of histones with poly(ADP-ribose), the extraction of histones from chromatin by noncovalent binding to poly(ADP-ribose) on poly(ADP-ribose) polymerase-1, poly ADP-ribosylation of telomeric repeat-binding factor-1 within telomeres, and deacetylation of histones by the sirtuins. These reactions produce a variety of localized effects in chromatin structure, and altered function in response to changes in niacin status may have dramatic effects on genomic stability, cell division and differentiation, and apoptosis.
Kirkland
James B
JB
Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada. jkirklan@uoguelph.ca
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry*; D004032:Diet; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D006657:Histones / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D009243:NAD / Q000096:biosynthesis / Q000378:metabolism; D009525:Niacin / Q000378:metabolism*; D009536:Niacinamide / Q000097:blood; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D009525:Niacin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D037761:Sirtuins