title: Structural genes of wheat and barley 5-methylcytosine DNA glycosylases and their potential applications for human health.
abstract: Wheat supplies about 20% of the total food calories consumed worldwide and is a national staple in many countries. Besides being a key source of plant proteins, it is also a major cause of many diet-induced health issues, especially celiac disease. The only effective treatment for this disease is a total gluten-free diet. The present report describes an effort to develop a natural dietary therapy for this disorder by transcriptional suppression of wheat DEMETER (DME) homeologs using RNA interference. DME encodes a 5-methylcytosine DNA glycosylase responsible for transcriptional derepression of gliadins and low-molecular-weight glutenins (LMWgs) by active demethylation of their promoters in the wheat endosperm. Previous research has demonstrated these proteins to be the major source of immunogenic epitopes. In this research, barley and wheat DME genes were cloned and localized on the syntenous chromosomes. Nucleotide diversity among DME homeologs was studied and used for their virtual transcript profiling. Functional conservation of DME enzyme was confirmed by comparing the motif and domain structure within and across the plant kingdom. Presence and absence of CpG islands in prolamin gene sequences was studied as a hallmark of hypo- and hypermethylation, respectively. Finally the epigenetic influence of DME silencing on accumulation of LMWgs and gliadins was studied using 20 transformants expressing hairpin RNA in their endosperm. These transformants showed up to 85.6% suppression in DME transcript abundance and up to 76.4% reduction in the amount of immunogenic prolamins, demonstrating the possibility of developing wheat varieties compatible for the celiac patients.
authors.affiliation: Department of Crop and Soil Sciences, Washington State University, Pullman, WA 99164, USA.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wen
authors.forename: Nuan
authors.initials: N
authors.lastname: Wen
authors.forename: Jinsong
authors.initials: J
authors.lastname: Pang
authors.forename: Gregor
authors.initials: G
authors.lastname: Langen
authors.forename: Rhoda A T
authors.initials: RA
authors.lastname: Brew-Appiah
authors.forename: Jaime H
authors.initials: JH
authors.lastname: Mejias
authors.forename: Claudia
authors.initials: C
authors.lastname: Osorio
authors.forename: Mingming
authors.initials: M
authors.lastname: Yang
authors.forename: Richa
authors.initials: R
authors.lastname: Gemini
authors.forename: Charles P
authors.initials: CP
authors.lastname: Moehs
authors.forename: Robert S
authors.initials: RS
authors.lastname: Zemetra
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Kogel
authors.forename: Bao
authors.initials: B
authors.lastname: Liu
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Wang
authors.forename: Diter
authors.initials: D
authors.lastname: von Wettstein
authors.forename: Sachin
authors.initials: S
authors.lastname: Rustgi
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002446:Celiac Disease / Q000178:diet therapy; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018899:CpG Islands; D045647:DNA Glycosylases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D018744:DNA, Plant / Q000235:genetics; D055050:Diet, Gluten-Free; D004044:Dietary Proteins / Q000009:adverse effects; D017343:Genes, Plant; D014644:Genetic Variation; D001467:Hordeum / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D010940:Plant Proteins / Q000009:adverse effects / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055315:Prolamins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D014908:Triticum / Q000009:adverse effects / Q000201:enzymology* / Q000235:genetics*
chemical_list: D018744:DNA, Plant; D004044:Dietary Proteins; D010940:Plant Proteins; D055315:Prolamins; C093335:5-methylcytosine-DNA glycosylase; D045647:DNA Glycosylases