Syndromes of disordered chromatin remodeling

Abstract

Syndromes of disordered ‘chromatin remodeling’ are unique in medicine because they arise from a general deregulation of DNA transcription caused by mutations in genes encoding enzymes which mediate changes in chromatin structure. Chromatin is the packaged form of DNA in the eukaryotic cell. It consists almost entirely of repeating units, called nucleosomes, in which short segments of DNA are wrapped tightly around a disk‐like structure comprising two subunits of each of the histone proteins H2A, H2B, H3 and H4. Histone proteins are covalently modified by a number of different adducts (i.e. acetylation and phosphorylation) that regulate the tightness of the DNA–histone interactions. Mutations in genes encoding enzymes that mediate chromatin structure can result in a loss of proper regulation of chromatin structure, which in turn can result in deregulation of gene transcription and inappropriate protein expression. In this review we present examples of representative genetic diseases that arise as a consequence of disordered chromatin remodeling. These include: α‐thalassemia/mental retardation syndrome, X‐linked (ATR–X); Rett syndrome (RS); immunodeficiency‐centromeric instability–facial anomalies syndrome (ICF); Rubinstein–Taybi syndrome (RSTS); and Coffin–Lowry syndrome (CLS).