Genome-Wide Atlas of Promoter Expression Reveals Contribution of Transcribed Regulatory Elements to Genetic Control of Disuse-Mediated Atrophy of Skeletal Muscle
Sergey S. Pintus,
Ilya R. Akberdin,
Ivan Yevshin,
Pavel Makhnovskii,
Oksana Tyapkina,
Islam Nigmetzyanov,
Leniz Nurullin,
Ruslan Devyatiyarov,
Elena Shagimardanova,
Daniil Popov,
Fedor A. Kolpakov,
Oleg Gusev,
Guzel R. Gazizova
Affiliations
Sergey S. Pintus
Laboratory of Bioinformatics, Federal Research Center for Information and Computational Technologies, 630090 Novosibirsk, Russia
Ilya R. Akberdin
Laboratory of Bioinformatics, Federal Research Center for Information and Computational Technologies, 630090 Novosibirsk, Russia
Ivan Yevshin
Laboratory of Bioinformatics, Federal Research Center for Information and Computational Technologies, 630090 Novosibirsk, Russia
Pavel Makhnovskii
Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow 123007, Russia
Oksana Tyapkina
Kazan Institute of Biochemistry and Biophysics FRC Kazan Scientific Center of RAS, 420007 Kazan, Russia
Islam Nigmetzyanov
Extreme Biology Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420009 Kazan, Russia
Leniz Nurullin
Kazan Institute of Biochemistry and Biophysics FRC Kazan Scientific Center of RAS, 420007 Kazan, Russia
Ruslan Devyatiyarov
Extreme Biology Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420009 Kazan, Russia
Elena Shagimardanova
Extreme Biology Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420009 Kazan, Russia
Daniil Popov
Institute of Biomedical Problems of the Russian Academy of Sciences, Moscow 123007, Russia
Fedor A. Kolpakov
Laboratory of Bioinformatics, Federal Research Center for Information and Computational Technologies, 630090 Novosibirsk, Russia
Oleg Gusev
Extreme Biology Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420009 Kazan, Russia
Guzel R. Gazizova
Extreme Biology Laboratory, Institute of Fundamental Medicine and Biology, Kazan Federal University, 420009 Kazan, Russia
The prevention of muscle atrophy carries with it clinical significance for the control of increased morbidity and mortality following physical inactivity. While major transcriptional events associated with muscle atrophy-recovery processes are the subject of active research on the gene level, the contribution of non-coding regulatory elements and alternative promoter usage is a major source for both the production of alternative protein products and new insights into the activity of transcription factors. We used the cap-analysis of gene expression (CAGE) to create a genome-wide atlas of promoter-level transcription in fast (m. EDL) and slow (m. soleus) muscles in rats that were subjected to hindlimb unloading and subsequent recovery. We found that the genetic regulation of the atrophy-recovery cycle in two types of muscle is mediated by different pathways, including a unique set of non-coding transcribed regulatory elements. We showed that the activation of “shadow” enhancers is tightly linked to specific stages of atrophy and recovery dynamics, with the largest number of specific regulatory elements being transcriptionally active in the muscles on the first day of recovery after a week of disuse. The developed comprehensive database of transcription of regulatory elements will further stimulate research on the gene regulation of muscle homeostasis in mammals.
