ABSTRACT
FSHD Facioscapulohumeral Muscular Dystrophy: Clinical Medicine and Molecular Cell Biology, edited by Meena Upadhyaya and David N.Cooper. © 2004 Garland/BIOS Scientific Publishers Limited, Abingdon.
9.1 Introduction
Classical genes only constitute a small part of the human nuclear genome alongside numerous repetitive elements of various sizes and copy numbers. Some of these are clustered in tandem repeat arrays, amplified by unequal crossover or unequal sister chromatid exchanges. Some constitute families of homologous sequences dispersed in the genome, are remnants of transposable elements that have integrated into various locations by mechanisms involving occasionally a DNA or more frequently an RNA intermediate. A few of these still encode the enzymes needed for their transposition, and a number of human mutations have been found to be caused by such insertional events (e.g. Sukarova et al., 2001). A cellular defense mechanism to prevent damage by active transposition is the methylation of CpG sequences in repeated elements (Walsh et al., 1998). This small chemical modification will contribute to heterochromatin assembly, a compact protein/DNA structure that inhibits transcription, recombination and transposition. A first step is the recruitment of methyl CpG-binding proteins that associate with histone deacetylases (HDACs). These enzymes target the acetylated lysines of the nucleosomal histones, restore their positive charges thereby increasing their ionic interactions with the phosphate groups of DNA. The resulting compacted nucleosomes will recruit histone H1 and non-histone proteins such as HP1 to further condense into heterochromatin (e.g. Saveliev et al., 2003).
