At the DNA-level, genes are regulated at their promoters, the sites in DNA where mRNA transcription starts. Many promoters are regulated by enhancers, DNA sequences that can be located far away from the promoter. A second layer of gene regulation involves the packaging of DNA with histone proteins to nucleosomes which are the building blocks of chromatin and chromosomes; genes in densely packaged chromatin are silent while those in open chromatin are active. Biochemical modifications of histones, such as acetylation and methylation, influence packaging of chromatin.