Structural genes of wheat and barley 5-methylcytosine DNA glycosylases and their potential applications for human health

Wen, Shanshan; Wen, Nuan; Pang, Jinsong; Langen, Gregor; Brew-Appiah, Rhoda A. T.; Mejias, Jaime H.; Osorio, Claudia; Yang, Mingming; Gemini, Richa; Moehs, Charles P.; Zemetra, Robert S.; Kogel, Karl-Heinz; Liu, Bao; Wang, Xingzhi; von Wettstein, Diter; et. al.

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.

Más información

Título según WOS: ID WOS:000312605600083 Not found in local WOS DB
Título de la Revista: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volumen: 109
Número: 50
Editorial: NATL ACAD SCIENCES
Fecha de publicación: 2012
Página de inicio: 20543
Página final: 20548
DOI:

10.1073/pnas.1217927109

Notas: ISI