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Regulation of Gene Expression in Eukaryotes:- Chromatin Is Remodeled by Acetylation and Nucleosomal Displacements

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  1103

2026-08-02

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Regulation of Gene Expression in Eukaryotes:- Chromatin Is Remodeled by Acetylation and Nucleosomal Displacements

The detailed mechanisms for transcription-associated structural changes in chromatin, called chromatin re modeling, are now coming to light, including identification of a variety of enzymes directly implicated in the process. These include enzymes that covalently modify the core histones of the nucleosome and others that use the chemical energy of ATP to remodel nucleosomes on the DNA (Table 28–2). The acetylation and deacetylation of histones figure prominently in the processes that activate chromatin for transcription. As noted above, the amino-terminal domains of the core histones are generally rich in Lys residues. Particular Lys residues are acetylated by histone acetyltransferases (HATs). Cytosolic (type B) HATs acetylate newly synthesized histones before the histones are imported into the nucleus. The subsequent assembly of the histones into chromatin is facilitated by additional proteins: CAF1 for H3 and H4, and NAP1 for H2A and H2B. (See Table 28–2 for an explanation of some of these abbreviated names.) Where chromatin is being activated for transcription, the Nucleosomal histones are further acetylated by nuclear (type A) HATs. The acetylation of multiple Lys residues in the amino-terminal domains of histones H3 and H4 can reduce the affinity of the entire nucleosome for DNA. Acetylation may also prevent or promote in teractions with other proteins involved in transcription or its regulation. When transcription of a gene is no longer required, the acetylation of nucleosomes in that vicinity is reduced by the activity of histone deacetylases, as part of a general gene-silencing process that restores the chromatin to a transcriptionally inactive state. In addition to the removal of certain acetyl groups, new covalent modification of histones marks chromatin as transcriptionally inactive. As an example, the Lys residue at position 9 in histone H3 is often methylated in heterochromatin. Chromatin remodeling also requires protein complexes that actively move or displace nucleosomes, hydrolyzing ATP in the process (Table 28–2). The enzyme complex SWI/SNF found in all eukaryotic cells, contains 11 polypeptides (total Mr 2X10⁶) that together create hypersensitive sites in the chromatin and stimulate the binding of transcription factors. SWI/SNF is not required for the transcription of every gene. NURF is another ATP-dependent enzyme complex that remodels chromatin in ways that complement and overlap the activity of SWI/SNF. These enzyme complexes play an important role in preparing a region of chromatin for active transcription.