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Unformatted text preview: BICD 130 Embryos, Genes, and Development Midterm Exam Pick-up
Jackie Vignes 4334 Bonner Hall (82)2-0654 10 AM - 4 PM Theory of Differential Gene Activity
The cells that descend from the zygote have different forms and functions because of differential utilization of the same genetic information Theory of Differential Gene Activity Genomic equivalence Differential utilization of genetic information Structure of a Typical Eukaryotic Gene (human -globin) The Flow of Information in Eukaryotic Gene Expression The Flow of Information in Eukaryotic Gene Expression Mechanisms of Differential Gene Activity Differential gene transcription Selective nuclear RNA processing Differential mRNA stability Selective mRNA translation Differential protein modification Differential protein stability Transcriptional Regulation The major mechanism for achieving differential gene activity Cells make differential use of the same genomic information by selectively transcribing only certain genes Different (though overlapping) sets for different cell types Transcriptional Enhancers Confer increased transcriptional activity on promoter of associated gene Activity is "independent" of distance, orientation, 5 or 3 placement The major source of tissue- and stagespecificity of gene expression Sites of binding of transcriptional regulatory proteins Separate enhancer modules direct tissue-specific expression of Drosophila yolk protein genes Activities of Transcription Factors Bind DNA sequence-specifically --DNA-binding domain Increase (activator) or decrease (repressor) frequency of transcription of gene --Co-activator or co-repressor recruitment domain [Form dimeric or other complexes with other DNA-binding proteins --Dimerization domain] Combinatorial action of transcription factors determines the tissue specificity of gene expression Chick 1 lens crystallin gene (eye) Rat somatostatin gene (pancreas) Transcriptional enhancers are modular Mouse Pax-6 gene -galactosidase Expression of reporter gene driven by eye enhancer (B) Transcriptional Enhancers Integrate multiple transcriptional inputs (both activating and repressing) into novel output Modular Silencer elements also contribute to spatial and temporal specificity of gene expression NRSE: Neural Restrictive Silencer Element L1 (cell adhesion protein) gene NRSE is bound by Neural Restrictive Silencer Factor (NRSF), a transcriptional repressor expressed everywhere outside of the nervous system MyoD induces muscle development Structure of a basic helix-loop-helix (bHLH) protein dimer bHLH proteins play essential roles in muscle and nervous system development Regional expression of Myf-5 and MyoD in the somite is induced by cell signaling Myf-5-lacZ reporter gene expression Muscle commitment and differentiation are controlled by the MyoD family of transcription factors
(MRF-4) Mechanisms of Differential Gene Activity Differential gene transcription Selective nuclear RNA processing Differential mRNA stability Selective mRNA translation Differential protein modification Differential protein stability RNA selection regulates which nuclear transcripts are processed into cytoplasmic mRNAs Nuclear RNA selection ("censoring") in the sea urchin larva Stable mRNA from the CyIIIa gene accumulates only in ectoderm, but introncontaining transcripts are present in nuclei of all three germ layers CyIIIa encodes a cytoplasmic actin Differential splicing generates distinct mRNAs from the same primary transcript Alternative splicing takes every possible form Alternative splicing of the primary transcript from the calcitonin/CGRP gene creates mRNAs for distinct proteins hormone neuropeptide Alternative splicing creates mRNAs for multiple isoforms of rat -tropomyosin The combinatorial potential of alternative splicing The Drosophila Dscam gene can theoretically produce 38,016 isoforms
Dscam (Down syndrome cell adhesion molecule) is involved in controlling axon targeting in the fly nervous system Mechanisms of Differential Gene Activity Differential gene transcription Selective nuclear RNA processing Differential mRNA stability Selective mRNA translation Differential protein modification Differential protein stability mRNA for the milk protein casein is stabilized in the presence of the hormone prolactin t1/2= 28.5 hrs t1/2= 1.1 hrs ...
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