Packaging principle: how DNA methylation and histone acetylation control the transcriptional activity of chromatin.

Chromatin contains DNA, the transcriptional machinery, and structural proteins such as histones. All these components together are necessary for the physiologic control of transcription. A consideration of recent advances leads to a packaging principle for gene regulation. This packaging principle states that the transcriptional activity of a gene is largely controlled by the packaging of the template within chromatin. This assumption follows from experiments that establish the covalent modification of chromatin as a major causal influence on gene activity. DNA methylation and histone acetylation alter the nucleosomal infrastructure to repress or activate transcription. These covalent modifications can have roles in both promoter-specific events and the global control of chromosomal activity. These regulatory functions are essential for vertebrate development.