Chromatin plasticity, control of gene expression and human disease

The nucleosome - an octamer of core histones surrounded by less than two tu rns of DNA - was recognized in the 1970s as the basic unit in chromatin, th e highly organized nucleoprotein material that contains the genetic informa tion in the nucleus of a eukaryotic cell. The accessibility of DNA in chrom atin is of utmost importance for gene transcription, DNA replication and re pair. Recently, protein complexes purified from nuclear extracts have been found endowed with the ability to remodel chromatin structure at a local le vel Each complex contains one molecule with ATPase activity. Using the ener gy of ATP, these complexes can modify the positioning and accessibility of nucleosomes, induce sliding of the histone octamer along the DNA or its tra nsfer to a different DNA fragment, a likely basis for their regulatory role in gene transcription. Recent findings indicate that a variety of human di seases could result from abnormalities in control processes operating at th e level of chromatin.