cellbio2 - lecture 1 corticosterone signaling -...

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lecture 1 corticosterone signaling - CBG=Corticosterone binding globulin – binds to cort in blood and keeps it soluble - chief cells – cells in epithelium that lines stomach; express cort receptor, secrete pepsinogen into stomach - cort receptor- (aka GR- gluco-corticoid receptor) - TAD – binds to “coactivators” and “nucleosome remodeling complexes” - DBD (DNA binding domain) – binds HREs(hormone response element) of cort-controlled genes, including HRE of pepsinogen gene - HRE – sequences that made specific genes sensitive to specific hormones; cort HRE regulates genes that are turned on in response to corticosterone - HBD – binds corticosterone; has NLS(nuclear localization signal) – NLS can direct import of proteins in nucleus - when cort receptor is not bound to cort, the NLS in the HBD is masked; when it is bound to cort, the NLS in the HBD is unmasked - pepsinogen gene – transcribed region of the gene encodes pepsinogen; gene has a core promoter at -1-50; gene also has cort HRE at -444; the HRE is bound by the DBD of cort receptor; it is this part of the gene that makes the gene responsive to cort - cort HRE is AGAACAATTTGTTCT – very specific region of DNA that will be bound to cort receptor - coactivators – proteins that: - bind to general transcription factors (eg, TFIID) - have “HAT” activity (histone acetyl transferase) – proteins with HAT activity attach acetyl groups to core histones - fcotylation of core histones weakens interaction of histone octamer with DNA, this is thought to facilitate nucleosome repositioning - nucleosome remodeling complexes – these protein complexes can reposition the nucleosomes with respect to the gene - general transcription factors, pol II (work as described previously) - other transcriptional machinery/transcription modifiers, translational machinery (as before) - process – stress happens – adrenal glands secrete corticosterone - in blood cort is bound be CBG, this keeps cort soluble in blood allowing it to circulate freely - upon encountering chief cells, cort passes through membrane and enters cell - cort binds to cort receptor in cytoplasm (cytosol) - binding of cort to cort receptor causes conformational change in receptor that exposes the NLS - exposure of NLS results in import of cort – cort receptor complex into nucleus - in nucleus, cort receptor binds HRE on target genes (including pepsinogen gene) - TAD recruits coactivators and nucleosome remodeling complexes to pepsinogen - these collaborate to promote transcription of pepsinogen gene - coactivators (via HAT activity); weaken octamer – DNA interactions making it easier for nucleosome remodeling complexes to move nucleosomes away from core promoter of pepsinogen gene - coactivators also recruit general transcription factors to gene, further accelerating onset of pepsinogen gene transcription - transcription of pepsinogen begins, transcript is processed, exported from nucleus, translated and secreted; is converted to pepsin in stomach – drives much
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This note was uploaded on 02/29/2012 for the course ZOOLOGY 570 taught by Professor Stretton during the Fall '10 term at Wisconsin.

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cellbio2 - lecture 1 corticosterone signaling -...

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