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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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| - | |}
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| - | ==== 1. Draw the Clock/Bmal1 in seperate and dimerized state ====
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| - | {{TutorialVideo|4QHuGmd1Tnk|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|aligncentery.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. Finally, group the two gene-product boxes. Now you have drawn the two states of the Bmal1 and Clock gene-products, the separate and dimerized state.
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| - | ==== 2. Draw the dimerization event ====
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| - | The actual event of dimerization is drawn by two curved arrows that point from the individual elements representing the separate states and the grouped element representing the dimerized state. First draw two straight arrows pointing to the Clock/Bmal1 complex, one from the separate Bmal1 element and one from the separate Clock element. You will notice that while you are moving a start or end point of a line near another element, little bulls eyes appear:
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| - | {|class=prettytable
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| - | |{{TutorialImage|linkanchors.png}}
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| - | |}
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| - | These objects are called link anchors and can be used to connect line ends to elements on the pathway. When you move the line end near a link anchor, it will snap on to it and the line will be connected to the corresponding shape. This means that the line will stick to the shape when you move it. You can release the connection by moving the line end away from the link anchor.
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| - | Notice that when you move over a group, the group boundaries will also show link anchors. For example, if you move the point over the Clock/Bmal1 complex, you will see connectors for the individual gene-product boxes and the group:
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| - | {|class=prettytable
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| - | !Connect to element within the group
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| - | !Connect to the group
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| - | |{{TutorialImage|connect_datanode.png}}
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| - | |{{TutorialImage|connect_group.png}}
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| - | |}
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| - | In this case we want to connect the end point of the lines to the group, since the line represents the transition from the separate protein to the dimer, which is represented by the group.
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| - | {{TutorialHint|It's good habit to connect the lines in your pathway wherever you can. It makes it easier to change the layout of the pathway in the future, because when you move an object, the connected lines will stick to it. Another advantage of defining connections is that it enables conversion to a graph. When the interactions between the entities in the pathway are explicitly defined, this information can be used for computational purposes. For example, the pathway can be converted to a Cytoscape network to perform various graph analysis algorithms (see http://www.cytoscape.org).}}
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| - | To make the two arrows more visually appealing, you can change their type. Here we will change the line type to 'curved', to create a connector that smoothly curves from the start to the end object. Change the line type of both lines by right clicking on the line and choosing '''Line type->curved'''. You will see that the line will now curve towards the Clock/Bmal1 complex.
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| - | {|class=prettytable
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| - | !Default line type
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| - | !After setting line type to 'curved'
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| - | |{{TutorialImage|clock_bmal1_straight.png}}
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| - | |{{TutorialImage|clock-bmal1-curved.png}}
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| - | |}
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| - | ==== 3. 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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