Spring 09 lecture 25

Spring 09 lecture 25 - 3. Concentrations and activities of...

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11 egg at start of development (just after fertilization); Maternal mRNA unevenly distributed throughout the embryo; cell division starts (daughter cells are getting/inheriting different maternal mRNAs) different set of proteins ( some are TFs ) synthesized in different poles of the embryo mRNA levels at zero hours – maternal mRNA translated hunchback bicoid nanos after 2 hours – zygotic mRNA transcribed a well: nanos and bicoid proteins (TF) control expression of hunchback (TF as well, control expression of other TFs) Bicoid positive regulator of hunchback transcription Nanos negative regulator of hunchback translation final result…. . hunchback bicoid nanos Example: Drosophila development (A-P orientation) 3. Concentrations and activities of TFs are regulated during cell differentiation and in response to hormones and signals from other cells
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22 3. Concentration and activities of TFs are regulated during cell differentiation and in response to hormones and signals from other cells Example 1 . Transcription of many TF is under regulation of extracellular signals - hormones Small, lipid soluble - steroid hormones Receptors for steroid hormones - nuclear receptors = TFs Cultured animal cells transfected with expression vectors encoding hybrid-proteins Antibodies to β -Gal for detection of the steroid hormone receptor constructs Steroid hormone (Dex)- dependent transport of the steroid hormone receptor (TF) to the nucleus
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33 3. Concentration and activities of repressors and activators are regulated during cell differentiation and in response to hormones and signals from other cells Example 2: Phosphorylation of serine or threonine residues regulates activity of some TFs It can lead to both (enhancing or decreasing DNA binding ability) Another possibility: TF already bound but inactive. Phosphorylation changes activation domain- enables it to stimulate transcription Signal transduction Growth factor ( extracellular 29 binds to receptor Receptor dimerization and cross- phosphorylation This is recognized by adapter GRB2 GRB2 binds to Sos Sos activates Ras Ras carries Raf to cell membrane Raf is activated Raf phosphorylates MAPKK MAPKK phosphorylates MAPK MAPK enters nucleus and phosphorylates Jun Jun associates with Fos into AP-1… Weaver: Molecular Biology
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44 4. Protection of active gene promoters from methylation Different molecular mechanisms of control of transcription initiation
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55 Deficiency of CG pairs in genome in general (ave 40%) - mostly present in some promoters - CG boxes (CpG islands ave 60%) Methyl groups are attached to C in some CG doublets on DNA 4. Protection of promoters of active genes from methylation Elimination of methylated C during evolution through conversion into T CpG islands in promoters of housekeeping genes are preserved as unmethylated → genes are active Accidental deamination of normal C repair system thinks it’s
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Spring 09 lecture 25 - 3. Concentrations and activities of...

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