Chapter Summary

There are three ways to regulate gene expression during development: transcriptional regulation, translational regulation, and posttranslational regulation [fig. 14.1]. Regulation of gene expression during development is due to a network of different interactions. Different developmental processes employ different strategies of regulation. Ultimately, all processes of development are due to regulation of gene expression using some or all of these three basic means.

Transcriptional regulation can occur by regulation at the level of chromatin structure [fig. 14.2], or at the basal promoter [fig. 14.3], or at other regulatory regions of a gene [figs. 14.4 and 14.5]. Modifications of chromatin render DNA accessible (euchromatin) or highly compacted and relatively inaccessible (heterochromatin) to the transcriptional apparatus and can occur by means of methylation, acetylation deacetylation, or recruitment of different nonhistone proteins to particular sites. Assembly of the transcriptional apparatus on the basal promoter is essential for transcription to occur, and this involves the association of RNA polymerase with basal transcription factors at the TATA box just upstream of the start site of transcription. Regulatory regions of a gene may contain binding sites for activators or suppressors, which can have long-range interactions with the basal promoter that influence transcription. The combinatorial effects of all of these elements determine the transcriptional state of a gene. Two examples of how complex interactions within a promoter regulate transcription can be seen in the endo10 regulatory region of the sea urchin [fig. 14.6] and the B-globin locus control region (LCR) [fig. 14.7].

Translational regulation can occur by regulation of transcript splicing [fig. 14.8], polyribosome formation [fig. 14.9], masking of mRNA transcript, regulating length of the poly-A tail, and mRNA localization [fig. 14.10]. Many genes contain introns that must be spliced out to form a mature mRNA that can be translated. Some genes also have alternately spliced isoforms that alter gene function, and the sex determination pathway is a good example of how a gene (double sex, dsx) can be regulated by differential splicing. In some species, translation does not occur until after the egg is activated by fertilization, and in sea urchins, this is largely due to the formation of polyribosomes necessary for translation of maternal mRNA. Also, mRNA can be "masked" in the cytoplasm by inhibitory proteins. Masked mRNA cannot be translated until it is "unmasked" and polyadenylated in the cytoplasm; this confers stability to the mRNA transcript. Localization of mRNA may also be necessary for translation, as in the case of nanos in Drosophila, where mRNA transcripts are repressed in some regions of the embryo and are translated in others. Frequently these interactions are regulated in the 3'UTR of a specific mRNA sequence.

Posttranslational regulation can occur via numerous protein modifications that may be necessary for proper function of a protein: nuclear localization, glycosylation, methylation, acetylation, phophorylation, and fatty acid modification, to mention some examples. Also, many proteins need to form a complex with other proteins before they can be functional. For example, active Hedgehog ligand is formed by autocatalytic cleavage followed by esterification, which may play a role in restricting diffusion of active Hedgehog ligand during development [fig. 14.11]. The restriction of diffusion by esterification may also be important in Sonic Hedgehog signaling from the notochord [fig. 14.12], and it is likely that posttranslational processing is important for the Hh family of ligands. Members of the TGF Bfamily of ligands (activin, Vg1, BMP) need to undergo proteolytic cleavage and dimerization in order to be active [fig. 14.13]. Proteins may also need to assemble into macromolecular complexes, as in the case of skeletal muscle fibers, or may need to experience cycles of degradation, called turnover, in order to function properly.


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