Chromatin Remodeling and Histone Modifications

DNA is compacted, folded and organized within chromatin in the nuclei of eukaryotic cells. As the fundamental subunit of chromatin, nucleosomes form a chain of small ellipsoidal beads of histone proteins around which the DNA is circumscribed. Four histones (H2A, H2B, H3, and H4) form the octamer center of the nucleosome with 146 nucleotide pairs wrapped around the center 1¾ turns. Each histone has an amino-terminal tail region consisting of 25-40 amino acid residues that protrude beyond the nucleosome surface.  H1 histone plays a role in linking the nucleosome structures together to condense chromatin.

Chromatin exists in many configurations and undergoes dynamic structural changes. These range from local changes necessary for transcriptional regulation to global changes necessary for chromosome segregation. Several epigenetic mechanisms introduce variation to chromatin structure, including covalent histone modifications, histone variant composition, DNA methylation, and Noncoding RNA.

These changes to the chromatin structure, called chromatin remodeling, may facilitate gene transcription by loosening the histone-DNA complex, allowing other proteins such as transcription factors access to the DNA. Alternatively, chromatin remodeling where the histone assumes a more closed confirmation blocks transcription factor access to the DNA, resulting in loss of gene expression. Relatively little is known about how remodeling factors change nucleosome structure and how different factors work together to promote chromatin remodeling. Chromatin remodeling is typically initiated by posttranslational modification of the amino acids that make up the histone proteins, as well as through methylation of neighboring DNA.

• Overview of DNA methylation
• Histone modifications, histone variants, and chromatin remodeling
• Workflows for chromatin immunoprecipitation