Epigenetic regulators and histone modification.

Epigenetic inheritance is a key element in the adaptation of organisms to a rapidly changing environment without stably changing their DNA sequence. The necessary changes in its gene expression profiles are frequently associated with variations in chromatin structure. The conformation of chromatin is profoundly influenced by the post-translational modification of the histone proteins, the incorporation of histone variants, the activity of nucleosome remodelling factors and the association of non-histone chromatin proteins. Although the hierarchy of these factors is still not fully understood, genetic experiments suggest that histone-modifying enzymes play a major causal role in setting up a particular chromatin structure. In this article, the recent progress that was made to understand the molecular mechanisms of the targeting and regulation of histone modifiers and its implication for epigenetic inheritance are reviewed.     

Chromatin Structure,Heterochromatin, and Transposable Genetic Elements: Are These Teammates?

Gene content proved to be less than expected in completely sequenced eukaryotic genomes. Moreover, gene number differs only three times between such distant organisms as human and Drosophila. Hence it is likely that the essential functional and structural differences between the two species mostly depend on the regulation of gene activity than on the set and quality of genes themselves. New data demonstrate that changes in chromatin structure play a greater role in the fine gene activity regulation than considered before. R.B. Khesin had foreseen many chromatin functions that only recently came to be recognized. Khesin was interested in genome inconstancy over his last years. A higher content of several important chromosomal proteins was recently revealed in chromatin of transposable genetic elements (TGE). The possible role of TGE in chromatin organization in the nucleus is considered.     

Mammalian chromodomain proteins: their role in genome organisation and expression

The chromodomain is a highly conserved sequence motif that has been identified in a variety of animal and plant species. In mammals, chromodomain proteins appear to be either structural components of large macromolecular chromatin complexes or proteins involved in remodelling chromatin structure. Recent work has suggested that apart from a role in regulating gene activity, chromodomain proteins may also play roles in genome organisation. This article reviews progress made in characterising mammalian chromodomain proteins and emphasises their emerging role in the regulation of gene expression and genome organisation. BioEssays 22:124-137, 2000.     

Interaction of SET domains with histones and nucleic acid structures in active chromatin

Changes in the normal program of gene expression are the basis for a number of human diseases. Epigenetic control of gene expression is programmed by chromatin modifications-the inheritable "histone code"-the major component of which is histone methylation. This chromatin methylation code of gene activity is created upon cell differentiation and is further controlled by the "SET" (methyltransferase) domain proteins which maintain this histone methylation pattern and preserve it through rounds of cell division. The molecular principles of epigenetic gene maintenance are essential for proper treatment and prevention of disorders and their complications. However, the principles of epigenetic gene programming are not resolved. Here we discuss some evidence of how the SET proteins determine the required states of target genes and maintain the required levels of their activity. We suggest that, along with other recognition pathways, SET domains can directly recognize the nucleosome and nucleic acids intermediates that are specific for active chromatin regions.