Molecular Biology:Seeing histone tails specifically
An explanation of the mechanism by which certain factors involved in gene regulation act specifically. . The study, which could ultimately provide a basis for new drug targets, reports on how some histone modifications are recognized within the cell.
DNA in the cell is wrapped around histones to form chromatin, whose structure is regulated by a complex array of factors, which together alter the accessibility and activity of the underlying packaged genes. Each histone has multiple sites that can be covalently modified, and these modifications are associated with distinct genomic activities, including whether the underlying genes are switched on or off.
Understanding how the enzymes that modify histones recognize their specific site, and either modify or remove modifications is a key goal in deciphering gene regulation. Raymond Trievel and colleagues report structures of two key regulators of histone modifications in the JMJD2 family bound to their target substrate sites, indicating how these enzymes recognize and thus remove modifications at particular sites. This starts to reveal the mechanism of specificity for factors involved in regulation of genes such as androgen hormone responsive targets, and may provide a basis for drug discovery, targeting this and other family members in diseases such as cancer.

Author contact:Raymond Trievel (University of Michigan, Ann Arbor, MI, USA)
Tel: +1 734 677 0928; E-mail: rtrievel@umich.edu