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| + | This page has been retired, current tutorial content is available [[Help:Tutorial|here]]. |
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| - | {{Template:TutorialNavigate|6}}
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| - | == Clock and Bmal1 dimerize and bind to the E-box element ==
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| - | To activate the target genes of the Circadian clock pathway, the Clock and Bmal1 proteins dimerize and the resulting heterodimer will bind to the E-box elements of the target genes to activate transcription. We are now going to draw this process in our pathway, making it look like this:
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| - | {|class=prettytable
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| - | |{{TutorialImage|clock_bmal1_binding.png}}
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| - | ==== 1. Draw the Clock/Bmal1 in seperate and dimerized state ====
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| - | {{TutorialVideo|NnSLTulGpVk|300|Drawing the dimerization and binding<br>to the E-box element}}
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| - | Drag the Clock and Bmal1 gene-products to position them above the previously drawn E-box illustration. Use the {{TutorialImage|aligncenterx.gif}} ''align horizontal center'' button to align the two gene-products horizontally. Now copy and paste the two elements and place them below each other, like in the image above. The bottom Clock/Bmal1 refers to the heterodimer and this is illustrated by stacking the two gene-product boxes horizontally. You can easily stack multiple elements by selecting them and clicking the {{TutorialImage|stackhorizontalcenter.gif}} ''stack horizontally'' button. Now you have drawn the two states of the Bmal1 and Clock gene-products, the seperate and dimerized state.
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| - | ==== 2. Draw the dimerization event ====
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| - | The actual event of dimerization is drawn by a brace and arrow. Draw a brace, using the {{TutorialImage|newbrace.gif}} ''brace'' button and resize it to match the brace in the image above. You will see that the brace initially has a wrong orientation, it points up instead of down. You can rotate the brace by dragging the ''rotation handle'' (green circle on the right of the brace). Rotate it 180 degrees to make it point down and put it in the right position. Now draw an arrow from the tip of the brace to the stacked Clock/Bmal1 dimer. Group the seperate Bmal1 and Clock gene-products together with the brace, so you can easily move them together. Also group the stacked Clock/Bmal1 dimer.
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| - | ==== 3. Connect the arrow ====
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| - | {{TutorialVideo|2g-Uh-Ni9ns|300|Connecting lines}}
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| - | In this step you are going to specify the connections of the arrow. The start point of the arrow should be connected to the group consisting of the Bmal1, Clock gene-products and brace, the end point should be connected to the Clock/Bmal1 dimer. To connect the a start/end point of a line to an object, drag the line's handle over the object, while holding the ALT key on the keyboard. The object will be highlighted in green as a notification that the point is now connected to that object. Now you can release the ALT key and move the point back to it's original position. The object will stop being highlighted, but the point stays connected. You can check whether you correctly connected the point by moving the object, the point should move along. Look at the movie on the right to see how it works. Now connect the start point of the arrow with the group consisting of the seperate Bmal1 and Clock gene-product and the brace. Connect the end point to the Clock/Bmal1 dimer.
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| - | {{TutorialHint|Specify connections for the lines in your pathway wherever you can. The advantage of specifying connections for all lines is that you can more easily edit the pathway, because the editor automatically adjusts the position of the line when you move one of the connected objects. This makes it easier to change the pathway in the future. Another advantage is that a pathway where the connections are specified properly can be converted to a Cytoscape network (see http://www.cytoscape.org).}}
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| - | ==== 4. The Clock/Bmal1 dimer binds to the E-box element ====
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| - | Finally we are going to draw how the Clock/Bmal1 binds to the E-box element. Copy the Clock/Bmal1 dimer and place the copy just above the E-box element. Now draw a line from the top dimer to the bottom dimer and connect the start and end points to the dimers.
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| - | {{Template:TutorialNavigate|6}}
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