The acetylation of histone proteins alters chromatin structure and permits some transcription factors to bind to DNA

Histone acetylation One factor affecting chromatin structure is acetylation, the addition of acetyl groups (CH3CO) to histone proteins. Histones in the octamer core of the nucleosome have two domains: (1) a globular domain that associates with other histones and the DNA and (2) a positively charged tail domain that probably interacts with the negatively charged phosphates on the backbone of DNA (i Figure 16.20).

Acetyl groups are added to histone proteins by acteyl-transferase enzymes; the acetyl groups destabilize the nu-cleosome structure, perhaps by neutralizing the positive charges on the histone tails and allowing the DNA to separate from the histones. Other enzymes called deacetylases strip acetyl groups from histones and restore chromatin repression. Certain transcription factors (see Chapter 13) and other proteins that regulate transcription either have acteyltransferase activity or attract acteyltransferases to the DNA.

Some transcription factors and other regulatory proteins are known to alter chromatin structure without acetylating histone proteins. These chromatin-remodeling complexes bind directly to particular sites on DNA and reposition the nucleosomes, allowing transcription factors to bind to promoters and initiate transcription.

DNA methylation Another change in chromatin structure associated with transcription is the methylation of cytosine bases, which yields 5-methylcytosine (see Figure 10.19). Heavily methylated DNA is associated with the repression of transcription in vertebrates and plants, whereas transcriptionally active DNA is usually unmethy-lated in these organisms.

DNA methylation is most common on cytosine bases adjacent to guanine nucleotides on the same strand (CpG); so two methylated cytosines sit diagonally across from each other on opposing strands:

DNA regions with many CpG sequences are called CpG islands and are commonly found near transcription start sites. While genes are not being transcribed, these CpG islands are often methylated, but the methyl groups are removed before the initiation of transcription. CpG meth-ylation is also associated with long-term gene repression, such as on the inactivated X chromosome of female mammals (see Chapter 4).

Recent evidence suggests an association between DNA methylation and the deacetylation of histones, both of which repress transcription. Certain proteins that bind tightly to methylated CpG sequences form complexes with other proteins that act as histone deacetylases. In other words, methylation appears to attract deacetylases, which remove acetyl groups from the histone tails, stabilizing the nucleosome structure and repressing transcription. De-methylation of DNA would allow acetyltransferases to remove these acetyl groups, disrupting nucleosome structure and permitting transcription.

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