Sandbox Reserved 973: Difference between revisions
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Nevertheless recents studies showed that every cell has its autonomy towards the circadian cycle and it is important to notice that the two genes Clock and Bmal1 are not identically expressed in every tissues and that the two proteins don't act the same way in this different cell types. Clock mRNA follow a transcriptional cycle in the peripheric oscillators whereas it is constitutively expressed in the SCN. Futhermore the different ROR proteins which have feedback effects on Bmal1 transcription are expressed in a tissue-specific manner, so BMAL1 has various functions at various moments. Again CLOCK doesn't have the same influence on downstream regulated genes depending on the tissue. For example , CLOCK has a limited impact on the amplitudes of the Rev-erbα mRNA oscillation in the SCN. But Clock−/− mice show a important decrease of the same amplitude in the liver. Thus it is important to keep in mind that the CLOCK:BMAL1 complex subunits are expressed in tissue-specific patterns and that the heterodimer makes a tissue-specific regulation of the circadian clock,which drive the study of the complex functions very difficult. | Nevertheless recents studies showed that every cell has its autonomy towards the circadian cycle and it is important to notice that the two genes Clock and Bmal1 are not identically expressed in every tissues and that the two proteins don't act the same way in this different cell types. Clock mRNA follow a transcriptional cycle in the peripheric oscillators whereas it is constitutively expressed in the SCN. Futhermore the different ROR proteins which have feedback effects on Bmal1 transcription are expressed in a tissue-specific manner, so BMAL1 has various functions at various moments. Again CLOCK doesn't have the same influence on downstream regulated genes depending on the tissue. For example , CLOCK has a limited impact on the amplitudes of the Rev-erbα mRNA oscillation in the SCN. But Clock−/− mice show a important decrease of the same amplitude in the liver. Thus it is important to keep in mind that the CLOCK:BMAL1 complex subunits are expressed in tissue-specific patterns and that the heterodimer makes a tissue-specific regulation of the circadian clock,which drive the study of the complex functions very difficult. | ||
The two peptides involved in the dimere have very similar sequences. In ''mus musculus''BMAL1 is 387 residues long and CLOCK is 361. | The two peptides involved in the dimere have very similar sequences . In ''mus musculus'' BMAL1 is 387 residues long and CLOCK is 361. | ||
Both of these subunits are basic helix-loop-helix-PAS proteins (bHLH-PAS) which | Both of these subunits are basic helix-loop-helix-PAS proteins (bHLH-PAS) which contain the same 3 particular domains: a bHLH domain, a PAS-A domain and a PAS-B domain. They are involved in DNA binding and dimerization abilities. Mutations that affects the heterodimer interfaces can then disturb the activity of the complex and therefore the persistence and periodicity of the circadian cycle. | ||
== Domains of the subunits == | == Domains of the subunits == | ||
This part deals with the structure of the 3 domains involved in the dimerization pattern. The transactivator domains of the two subunits which are both transcription factors working as positive elements in the circadian molecular clock will not be presented here. | |||
=== bHLH domain=== | === bHLH domain=== | ||
