Charting histone modifications and the functional organization of mammalian genomes

• Published in: Nature reviews. Genetics Vol. 12; no. 1; pp. 7 - 18
• Main Authors: Zhou, Vicky W., Goren, Alon, Bernstein, Bradley E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2011; Nature Publishing Group
• Subjects: 631/208/726; 631/337/100/2285; 631/337/386; Agriculture; Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chromatin - metabolism; Chromatin - ultrastructure; DNA; DNA methylation; DNA sequencing; Gene Function; Genome; Genomes; Histones; Histones - genetics; Histones - metabolism; Human Genetics; Humans; Medical research; Methylation; Mice; Nucleotide sequencing; Physiological aspects; Protein Processing, Post-Translational - genetics; Regulation; Regulatory Sequences, Nucleic Acid; review-article; RNA polymerase; Transcription factors; United States; United States > US; Massachusetts
• ISSN: 1471-0056; 1471-0064; 1471-0064
• DOI: 10.1038/nrg2905

Key Points Large-scale mapping of chromatin features has emerged as a powerful tool to understand the global landscape of genome regulation. In particular, chromatin immunoprecipitation followed by sequencing (ChIP–seq) has generated vast amounts of data on the genome-wide distribution of histone modifications across various cell types. Eukaryotic chromatin structure can be viewed as superimposed organizational layers, from DNA sequence, to nucleosomes, to histone modifications and variants and, finally, to higher-order structures. Histone modifications demarcate functional elements, including promoters, gene bodies, enhancers and boundary elements, in the large expanse of the mammalian genome. Promoters are subject to distinct chromatin patterns and regulation according to their CpG content. Namely, high CpG content promoters assume an active conformation by default and low CpG content promoters are inactive by default. Histone modifications may fine-tune the activities of promoters, gene bodies and enhancers, and the stability of repressive domains. Emerging evidence suggests that there are global correspondences between histone modification patterns, replication timing and higher-order nuclear structures. The amount of genome-scale data on covalent histone modification patterns is rapidly increasing. This Review brings together current knowledge on how modification 'signatures' relate to the structure and function of chromatin, from regulatory elements and gene structure to organization in the nucleus. A succession of technological advances over the past decade have enabled researchers to chart maps of histone modifications and related chromatin structures with increasing accuracy, comprehensiveness and throughput. The resulting data sets highlight the interplay between chromatin and genome function, dynamic variations in chromatin structure across cellular conditions, and emerging roles for large-scale domains and higher-ordered chromatin organization. Here we review a selection of recent studies that have probed histone modifications and successive layers of chromatin structure in mammalian genomes, the patterns that have been identified and future directions for research.