Research output: Contribution to journal › Article › peer-review
Genome-wide atlas of promoter expression reveals contribution of transcribed regulatory elements to genetic control of disuse-mediated atrophy of skeletal muscle. / Pintus, Sergey S.; Akberdin, Ilya R.; Yevshin, Ivan et al.
In: Biology, Vol. 10, No. 6, 557, 06.2021.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Genome-wide atlas of promoter expression reveals contribution of transcribed regulatory elements to genetic control of disuse-mediated atrophy of skeletal muscle
AU - Pintus, Sergey S.
AU - Akberdin, Ilya R.
AU - Yevshin, Ivan
AU - Makhnovskii, Pavel
AU - Tyapkina, Oksana
AU - Nigmetzyanov, Islam
AU - Nurullin, Leniz
AU - Devyatiyarov, Ruslan
AU - Shagimardanova, Elena
AU - Popov, Daniil
AU - Kolpakov, Fedor A.
AU - Gusev, Oleg
AU - Gazizova, Guzel R.
N1 - Funding Information: Funding: This research was funded by the Russian Foundation for Basic Research (RFBR), grant number 17-00-00308K (17-00-00242, 17-00-00296, 17-00-00243), the atlas integration into the GTRD database was supported by Russian Science Foundation (RSF), grant 19-14-00295. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Atrophy
KW - Cis-regulatory elements
KW - Disuse
KW - Enhancers
KW - Promoters
KW - Rat
KW - RNA transcription
KW - Skeletal muscles
KW - Transcribed non-coding elements of genome
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85108966136&partnerID=8YFLogxK
U2 - 10.3390/biology10060557
DO - 10.3390/biology10060557
M3 - Article
C2 - 34203013
AN - SCOPUS:85108966136
VL - 10
JO - Biology
JF - Biology
SN - 2079-7737
IS - 6
M1 - 557
ER -
ID: 34032315