Transcriptional and Chromatin Dynamics of Muscle Regeneration after Severe Trauma

Carlos A. Aguilar, Ramona Pop, Anna Shcherbina, Alain Watts, Ronald W. Matheny, Davide Cacchiarelli, Woojin M. Han, Eunjung Shin, Shadi A. Nakhai, Young C. Jang, Christopher T. Carrigan, Casey A. Gifford, Melissa A. Kottke, Marcella Cesana, Jackson Lee, Maria L. Urso, Alexander Meissner

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Following injury, adult skeletal muscle undergoes a well-coordinated sequence of molecular and physiological events to promote repair and regeneration. However, a thorough understanding of the in vivo epigenomic and transcriptional mechanisms that control these reparative events is lacking. To address this, we monitored the in vivo dynamics of three histone modifications and coding and noncoding RNA expression throughout the regenerative process in a mouse model of traumatic muscle injury. We first illustrate how both coding and noncoding RNAs in tissues and sorted satellite cells are modified and regulated during various stages after trauma. Next, we use chromatin immunoprecipitation followed by sequencing to evaluate the chromatin state of cis-regulatory elements (promoters and enhancers) and view how these elements evolve and influence various muscle repair and regeneration transcriptional programs. These results provide a comprehensive view of the central factors that regulate muscle regeneration and underscore the multiple levels through which both transcriptional and epigenetic patterns are regulated to enact appropriate repair and regeneration.

Original languageEnglish
Pages (from-to)983-997
Number of pages15
JournalStem Cell Reports
Volume7
Issue number5
DOIs
StatePublished - 8 Nov 2016
Externally publishedYes

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