Inherited GPI deficiency: a disorder of histone hypoacetylation.
Τίτλος | Inherited GPI deficiency: a disorder of histone hypoacetylation. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Georgiou, E., Layton M., & Karadimitris A. |
Journal | Birth Defects Res C Embryo Today |
Volume | 87 |
Issue | 4 |
Pagination | 327-34 |
Date Published | 2009 Dec |
ISSN | 1542-9768 |
Λέξεις κλειδιά | Acetylation, Animals, Carbohydrate Metabolism, Inborn Errors, Embryonic Development, Epigenesis, Genetic, Female, Genes, Recessive, Glycosylphosphatidylinositols, Histone Deacetylase Inhibitors, Histones, Humans, Male, Mannosyltransferases, Membrane Proteins, Models, Biological, Mutation, Pregnancy, Promoter Regions, Genetic, Sp1 Transcription Factor |
Abstract | Co-operative interaction of transcription factors (TF) with epigenetic processes, such as chromatin remodeling and modification (acetylation or methylation), as well as DNA methylation, determine transcriptional activity, activation or repression of a given gene. Mutations disrupting binding of TF to their cognate DNA motifs would be expected to alter the epigenetic landscape of the promoter and selectively affect transcription of the given gene. We review here the transcriptional, epigenetic, biochemical, and clinical consequences of a constitutional mutation in the promoter of PIGM, a housekeeping gene that disrupts binding of the general TF, SP1, thus causing the autosomal recessive disease, inherited glycosylphosphatidylinositol (GPI) deficiency. We suggest that detailed dissection of the function of the mutated PIGM promoter provides important lessons pertinent to the transcriptional and epigenetic control of housekeeping genes as a whole and might have wider therapeutic implications. |
DOI | 10.1002/bdrc.20166 |
Alternate Journal | Birth Defects Res C Embryo Today |
PubMed ID | 19960552 |
Grant List | / / Medical Research Council / United Kingdom |