Histone-modifying enzymes
The packaging of the eukaryotic genome into highly condensed chromatin makes it inaccessible to the factors required for gene transcription, DNA replication, recombination and repair. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by the chromatin. The nucleosome is composed of an octamer of the four core histones around which 146 base pairs of DNA are wrapped. Several distinct classes of enzyme can modify histones at multiple sites. The figure on the right enlists those histone-modifying enzymes whose specificity has been determined. There are at least eight distinct types of modifications found on histones. Enzymes have been identified for acetylation,
methylation, demethylation, phosphorylation,
ubiquitination, O-GlcNAcylation, sumoylation,
ADP-ribosylation,
deimination, and
proline isomerization. For a detailed example of histone modifications in transcription regulation see RNA polymerase control by chromatin structure and table "Examples of histone modifications in transcriptional regulation". Different physiological changes are known to be associated with behavioural changes. In a 2009 review article, authors have summarized different studies of the histone acetyltransferases p300 and Rtt109, and the histone lysine demethylases LSD1 and JMJD2A. Additionally, recent evidences show the importance of HDACs in regulation of lipid metabolism and other metabolic pathways playing role in the pathophysiology of metabolic disorders.
