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Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational

Eukaryotic transcription must be activated by binding of transcription factors

Enhancers are regulatory regions located some distance away from the promoter

Proteins that help bend DNA can play an important role in transcription Fig 11.14

DNA bends to bring different areas in to close contact.

Enhancer-blocking insulators prevent enhancer activation Fig 11.17

Fig Insulators block the folding of DNA preventing enhancers from interacting with the promoter

How do eukaryotic cells jointly express several proteins (without operons)?

Promoter sequences where transcription factors can bind activating multiple gene in response to the environment

Fig Combinations of regulatory transcription factors regulate expression of different genes

Promoters typically have several regulatory sequences

Steroid response element

Steroids bind to receptors/transcription factors inside cell get translocated to the nucleus bind to promoters and activate transcription. cytoplasm

Steroid response element

Fig 16.1 Gene Expression is controlled at all of these steps: DNA packaging Transcription RNA processing and transport RNA degradation Translation Post-translational

Fig Alternate Splicing in Drosophila sex determination

Fig Alternate splicing leads to sex determination in fruit flies

Mammalian mRNA Splice-Isoform Selection Is Tightly Controlled Jennifer L. Chisa and David T. Burke Genetics, Vol. 175: , March 2007 Regulation of gene expression is often in response to a changing environment. But how stable can alternative splicing be, and does it play a role in maintaining homeostasis?

Alternative splicing modifies at least half of all primary mRNA transcripts in mammals. More than one alternative splice isoform can be maintained concurrently in the steady state mRNA pool of a single tissue or cell type, and changes in the ratios of isoforms have been associated with physiological variation and susceptibility to disease. Splice isoforms with opposing functions can be generated; for example, different isoforms of Bcl-x have pro-apoptotic and anti-apoptotic function. Chisa, J. L. et al. Genetics 2007;175: Fig. 1

Using RT-PCR alternatively spliced versions of different genes were identified

Chisa, J. L. et al. Genetics 2007;175: Fig. 4 variation in splice-isoform ratios is conserved in two genetically diverse mouse populations Black= genetically heterogeneous population UMHET3 Red= a population of hybrid females

Chisa, J. L. et al. Genetics 2007;175: Fig. 5 In different individuals splice isoforms in different tissues are conserved

Chisa, J. L. et al. Genetics 2007;175: Fig. 6 Splice-isoform ratios differ between young and old animals (different environments)

Conclusions: Differences are observed in different tissues and at different ages, but there was always tight control of the relative amounts of the different splice-isoforms. Slight differences in alternative splicing may be indicative of abnormalities (disease).