Slide 1Slide 2Slide 3Slide 4Slide 5Slide 6Slide 7Slide 8Slide 9Slide 10Slide 11Slide 12Slide 13Slide 14Slide 15Slide 16Slide 17Slide 18Slide 19Slide 20Slide 21Slide 22Slide 23Slide 24Slide 25Slide 26Slide 27Slide 28Slide 29Slide 30Slide 31Slide 32Slide 33Slide 34Slide 35Gene regulation in eukaryotes, Part IIMap of transcription factor binding sites in the regulatory region of the sea urchin gene endo-16. The regulatory regions of eukaryotic genes are often complex, and contain hundreds or thousands of binding sites for specific transcription factors.Much like we saw with the lac operon in E. coli:•the presence or absence of each transcription factor provides the gene with information about the state of the cell and/or its environment;•the regulatory region integrates this information to determine the transcription rate of that gene.Synergy of inputs1 2 3BA CFor some genes, multiple signals - represented by multiple transcription factors - must be present simultaneously for transcription to occur. This is known as synergy. TranscriptionInputsA, B, or C aloneA+B, A+C, or B+CA+B+Cnonenone or lowhighTFsEnhancersIn the sea squirt Ciona (right) the gene MesP is only expressed in the embryonic precursors of the heart.Transcription of MesP requires the simultaneous presence of two transcription factors, Tbx6b/c and Lhx3. Each of these TFs is expressed in a large portion of the embryo, but the only place they overlap is in the heart precursor cells … where they synergize to activate MesP transcription.Heart precursor cellsHeart precursor cellsGutTailmuscleTailmuscleWatson, Box 21-4, Fig. 14.5 hour embryosCiona larva121212Tbx6b/cTbx6b/cLhx3Lhx3OFFOFFONMesPTranscriptionModularity of regulation1 2 3For other genes, different enhancers can activate transcription independently in response to different transcription factors. Such promoters are said to be modular.BA C TranscriptionInputsneither A, B, or CA, B, or C alonenoyesadapted from Watson, Box 21-7, Fig. 1The Pitx1 gene of mice and humans encodes a protein that is essential for the development of four different organs. Within each organ, Pitx1 transcription is activated by a different tissue-specific enhancer in response to transcription factor(s) unique to that organ.TRANSCRIPT9 day mouse embryo (side) 10 day mouse embryo (dorsal)121212ON in thymusON in hindlimbON in olfactory pitAB3C33Due to the modular organization of its enhancers, the Pitx1 transcription unit can be activated by different transcription factors in different tissues.Expression of peptide hormones in human pancreas.Feather specification in a chicken embryo.Differential gene expression is a key component of how cells differentiate from one another in multicellular organisms.•With relatively few exceptions, all of the cells in the body share the same set of genes. They inherited these genes from the time that the individual was a fertilized egg.•Individual cells only express a subset of their genes as RNA or protein at any given time.•Different types of cells express different subsets of their genes.Skeletal muscle cells are specialized for contraction. They express muscle-specific cytoskel-etal proteins that allow the cell to contract when it receives the appropriate signals.Nerve cells are specialized for the conduction and integration of electrical signals. They express nerve-specific synaptic proteins that allow them to communicate these signals with other cells.CELL DIFFERENTIATIONHuman genomeapprox. 20,000 protein-coding genesHuman genomeSubset of genestranscribedin muscleNOTE: Some “housekeeping genes” are expressed by all cells. However, the majority of human genes are only expressed in certain cell types.Subset of genestranscribed innerve cellsExpression of peptide hormones in human pancreas.Feather specification in a chicken embryo.The primary reason that different cells transcribe different genes is that they contain different sets of transcription factors.But transcription factors themselves are gene products. How do cells acquire different transcription factors in the first place?During embryonic development the body arises from a fertilized egg with a single nuclear genome.There is no transcription at the time of fertilization. Rather, differential gene expression begins as the embryo divides into multiple cells.Watson, Fig. 21-1Three general strategies for initiating differential gene expression in embryosMaternally derived transcription factors are localized in the egg.Contact-mediated intercellular signals activate gene expression exclusively in the receiving cell.Secreted signaling molecules activate gene expression in receiving cells, and the concentration of that signal deter-mines which genes get activated.Maternal gene productsIn both animals and plants, fertilization involves the fusion of a very small sperm cell (in essence, a DNA delivery vehicle) and a very large egg cell that contains huge quantities of•RNA•protein •nutrients (e.g. yolk)The RNA and protein contained within the egg were produced by the mother's genome during the process of egg formation, and are referred to as maternal gene products.In the sea squirt, the gene Macho-1 encodes a zinc finger transcription factor that plays a critical role in formation of embryonic tail muscles. However, it is not the embryo's own Macho-1 gene that is used. Rather, the mother squirt transcribes her Macho-1 genes during egg formation.Gutcompare Watson, Fig. 21-7unfertilized egg mid-meiosis late meiosis 8 cell embryo (sideview)Cell B4.1Cell B4.1The Macho-1 mRNA is at first widely distributed, but during meiosis becomes concentrated first at the bottom of the egg (phase 1) and then moved to the posterior side (phase 2). When the embryo divides, only 2 of 8 cells will inherit Macho-1 mRNA.12All cells contain a set of muscle differentiation genes.But only the B4.1 cells inherit Macho-1 RNA and therefore synthesize Macho-1 protein (RED).OFFOFFOFFOFFOFFOFFOFFOFFOFFONONONThe Macho-1 TF selectively activates expression of muscle-specific proteins YELLOW in this cell.Remember ...Only a subset of genes will have binding sites for - and hence be regulated by -