title: Lessons from two human chromatin diseases, ICF syndrome and Rett syndrome.
abstract: Spatial organisation of DNA into chromatin profoundly affects gene expression and function. The recent association of genes controlling chromatin structure to human pathologies resulted in a better comprehension of the interplay between regulation and function. Among many chromatin disorders we will discuss Rett and immunodeficiency, centromeric instability and facial anomalies (ICF) syndromes. Both diseases are caused by defects related to DNA methylation machinery, with Rett syndrome affecting the transduction of the repressive signal from the methyl CpG binding protein prototype, MeCP2, and ICF syndrome affecting the genetic control of DNA methylation, by the DNA methyltransferase DNMT3B. Rather than listing survey data, our aim is to highlight how a deeper comprehension of gene regulatory web may arise from studies of such pathologies. We also maintain that fundamental studies may offer chances for a therapeutic approach focused on these syndromes, which, in turn, may become paradigmatic for this increasing class of diseases.
authors.affiliation: Institute of Genetics and Biophysics, A.Buzzati Traverso, Consiglio Nazionale delle Ricerche, via P.Castellino 111, 80131 Naples, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Matarazzo
authors.forename: M L
authors.initials: ML
authors.lastname: De Bonis
authors.forename: M
authors.initials: M
authors.lastname: Vacca
authors.forename: F
authors.initials: F
authors.lastname: Della Ragione
authors.forename: M
authors.initials: M
authors.lastname: D'Esposito
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D002869:Chromosome Aberrations; D019175:DNA Methylation; D005146:Facial Asymmetry / Q000235:genetics; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008958:Models, Molecular; D015518:Rett Syndrome / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
chemical_list: D002843:Chromatin