Signal Transduction via Nuclear Receptors

Nuclear receptors are transcription factors that regulate the frequency and accuracy of transcription initiation. Therefore, nuclear receptors interact with the general transcription factors (GTFs) and RNA polymerase II that assemble at the promoter, which is a specific DNAsequence most often found just upstream of a gene (also see Chap. 7.4). Generally, interactions between transcription factors and the GTF-polymerase complex are mediated, at least in part, by coactivator or corepressor proteins (Fig. 4.3). Coactivator proteins activate gene transcription by increasing the efficiency with which the GTF-polymerase complex assembles at promoter region of the gene. Conversely, core-pressor proteins inhibit transcription.

Coactivators increase transcription in several different ways. Some coac-tivators alter nucleosome structure. The promoter region of a gene often is inaccessible to the GTF-polymerase complex because the DNAis wrapped around a core of histone proteins or is associated with other proteins.

Figure 4.3 Regulation of gene transcription by ligand-activated receptors (R). Ligand-activated receptors (R) bind to specific DNA sequences (i.e., response elements, RE) and recruit various coactivator or corepressor proteins. For details, see Sec. 4.3.

One group of coactivators forms histone-modification complexes that can facilitate transcription by modifying histones and other chromatin proteins. For example, coactivators such as SRC (steroid-receptor coac-tivator), p300/CBP (CREB binding protein), and PCAF (p300/CBP-associated factor) have histone acetyltransferase (HAT) activity and add acetyl groups to lysine residues in histones (Fig. 4.3). Acetylation negates positive charges on histones and loosens their binding to DNA. Coactivators such as the coactivator-associated arginine methyltrans-ferase (CARM) express arginine methyltransferase activity, and increase transcription by adding methyl groups to arginines in histones and in other proteins.

A second group of coactivators forms chromatin-remodeling complexes that use ATP to make DNA available for transcription. One example of a chromatin-remodeling complex is the switching mating types/sucrose nonfermenting (SWI/SNF) family of proteins. The actions exerted by this complex are unclear, but they may involve histone sliding or simply a loosening of the association between DNA and histones.

Finally, a third group of coactivators forms mediator complexes that link transcription factors to the GTF-polymerase complex. An example of a mediator complex is the TRAP/DRIP (thyroid hormone receptor-associated protein/vitamin D receptor interacting protein) complex. This mediator complex acts as an adaptor that allows transcription factors to communicate with the GTF-polymerase complex. Categorization of coactivators as histone-modifiers, chromatin-remodelers, or mediators is somewhat arbitrary because coactivators can exert multiple functions.

Addiction To Nutrition

Addiction To Nutrition

Get All The Support And Guidance You Need To Be A Success At Beating Addictions With Nutrition. This Book Is One Of The Most Valuable Resources In The World When It Comes To A Definitive Guide To Unchain Addiction The Smarter And Healthy Way.

Get My Free Ebook

Post a comment