Difference between revisions of "Key master regulators of co-expressed genes"
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| − | Using advantages of the design of the experiment allowing time-series style analysis, we identified master regulators and key-nodes (master regulators with positive feedback loop) from clusters of co-expressed genes and reconstructed diagrams of interactions between master regulators, transcription factors, and target genes for the top five master regulators[8]. | + | Using advantages of the design of the experiment allowing time-series style analysis, we identified master regulators and key-nodes (master regulators with positive feedback loop) from clusters of co-expressed genes and reconstructed diagrams of interactions between master regulators, transcription factors, and target genes for the top five master regulators [8]. |
| − | We found that the main regulatory clusters were similar in both slow and fast muscles, but several unique patterns were discovered for each muscle type. In slow muscle, clusters were governed by regulators of proteasomal degradation and cell cycle regulators (see Supplementary Figure X). In particular, the most of regulators in slow muscle correspond to several E3 ubiquitin ligases (MAFbx/atrogin 1, Parkin) and components or regulators of SCF ubiquitin ligase complex (CUL1, SKP1, DDB1, ROC1, Ubs14) which are known signatures of disuse muscle atrophy in mammals as well as in humans[8,9]. | + | We found that the main regulatory clusters were similar in both slow and fast muscles, but several unique patterns were discovered for each muscle type. In slow muscle, clusters were governed by regulators of proteasomal degradation and cell cycle regulators (see Supplementary Figure X). In particular, the most of regulators in slow muscle correspond to several E3 ubiquitin ligases (MAFbx/atrogin 1, Parkin) and components or regulators of SCF ubiquitin ligase complex (CUL1, SKP1, DDB1, ROC1, Ubs14) which are known signatures of disuse muscle atrophy in mammals as well as in humans [8,9]. |
In the fast muscle, proteasomal degradation and cell cycle regulators also played an important role, but the master regulators, transcription factors and target genes were different (see Supplementary Figure X). Unlike the slow muscle, calpain-2, for example, acts as one of the crucial master-regulators in fast muscles. Calpains are the members of calcium-dependent proteolytic system which along with ubiquitin-proteasomal system is an important player in muscle atrophy mechanism ((Taillandier et al. 1996; Murphy 2010; Huang and Forsberg 1998); | In the fast muscle, proteasomal degradation and cell cycle regulators also played an important role, but the master regulators, transcription factors and target genes were different (see Supplementary Figure X). Unlike the slow muscle, calpain-2, for example, acts as one of the crucial master-regulators in fast muscles. Calpains are the members of calcium-dependent proteolytic system which along with ubiquitin-proteasomal system is an important player in muscle atrophy mechanism ((Taillandier et al. 1996; Murphy 2010; Huang and Forsberg 1998); | ||
To summarize, using the atlas and time-series design of analysis we demonstrated that several genes that were known for their involvement in muscle biology act as master regulators in genetic response to atrophy. | To summarize, using the atlas and time-series design of analysis we demonstrated that several genes that were known for their involvement in muscle biology act as master regulators in genetic response to atrophy. | ||
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| + | ==Description of master regulators in slow and fast muscles== | ||
Revision as of 21:25, 2 March 2021
Using advantages of the design of the experiment allowing time-series style analysis, we identified master regulators and key-nodes (master regulators with positive feedback loop) from clusters of co-expressed genes and reconstructed diagrams of interactions between master regulators, transcription factors, and target genes for the top five master regulators [8].
We found that the main regulatory clusters were similar in both slow and fast muscles, but several unique patterns were discovered for each muscle type. In slow muscle, clusters were governed by regulators of proteasomal degradation and cell cycle regulators (see Supplementary Figure X). In particular, the most of regulators in slow muscle correspond to several E3 ubiquitin ligases (MAFbx/atrogin 1, Parkin) and components or regulators of SCF ubiquitin ligase complex (CUL1, SKP1, DDB1, ROC1, Ubs14) which are known signatures of disuse muscle atrophy in mammals as well as in humans [8,9]. In the fast muscle, proteasomal degradation and cell cycle regulators also played an important role, but the master regulators, transcription factors and target genes were different (see Supplementary Figure X). Unlike the slow muscle, calpain-2, for example, acts as one of the crucial master-regulators in fast muscles. Calpains are the members of calcium-dependent proteolytic system which along with ubiquitin-proteasomal system is an important player in muscle atrophy mechanism ((Taillandier et al. 1996; Murphy 2010; Huang and Forsberg 1998);
To summarize, using the atlas and time-series design of analysis we demonstrated that several genes that were known for their involvement in muscle biology act as master regulators in genetic response to atrophy.
