Key Concepts of Section 9.6

• The activities of many transcription factors are indirectly regulated by binding of extracellular proteins and peptides to cell-surface receptors. These receptors activate intracellular signal transduction pathways that regulate specific transcription factors through a variety of mechanisms discussed in Chapter 16.

• Nuclear receptors constitute a superfamily of dimeric C4 zinc-finger transcription factors that bind lipid-soluble hormones and interact with specific response elements in DNA (see Figures 9-42 and 9-44).

• Hormone binding to nuclear receptors induces conformational changes that modify the interactions of these receptors with other proteins (see Figure 9-31b, c).

• Heterodimeric nuclear receptors (e.g., those for retinoids, vitamin D, and thyroid hormone) are found only in the nucleus. In the absence of hormone, they repress transcription of target genes with the corresponding response element. When bound to their ligands, they activate transcription.

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  Steroid hormone receptors are homodimeric nuclear receptors. In the absence of hormone, they are trapped in the cytoplasm by molecular chaperones. When bound to their ligands, they can translocate to the nucleus and activate transcription of target genes (see Figure 9-45).

• DNase I hypersensitive sites (DHSs) indicate the positions of transcription-factor binding in chromatin, although they do not indicate which transcription factor is bound. Nonetheless, mapping of DHSs in differentiating cells gives an overview of how transcription-factor-binding sites change as a cell differentiates into a specific cell type.

• In metazoans, RNA polymerase II often pauses during elongation within approximately 50–100 base pairs from the transcription start site. Release from this pause contributes to the regulation of gene transcription.

• Resumption of elongation by Pol II paused in the promoter-proximal region is also required for gene transcription and is a regulated step.

• In most cases, Pol II does not terminate transcription until after a sequence is transcribed that directs cleavage and polyadenylation of the RNA.