title: Transcriptional and Chromatin Dynamics of Muscle Regeneration after Severe Trauma.
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.
authors: Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA 02127, USA. Electronic address: carlos.aguilar@ll.mit.edu.
authors: Carlos A
authors: CA
authors: Aguilar
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors: Ramona
authors: R
authors: Pop
authors: Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA 02127, USA.
authors: Anna
authors: A
authors: Shcherbina
authors: Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA 02127, USA.
authors: Alain
authors: A
authors: Watts
authors: Military Performance Division, United States Army Institute of Environmental Medicine, Natick, MA 01760, USA.
authors: Ronald W
authors: RW
authors: Matheny
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors: Davide
authors: D
authors: Cacchiarelli
authors: Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA; Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Woojin M
authors: WM
authors: Han
authors: Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Eunjung
authors: E
authors: Shin
authors: Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA; Wallace Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Shadi A
authors: SA
authors: Nakhai
authors: Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332, USA; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA; Wallace Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Young C
authors: YC
authors: Jang
authors: Military Performance Division, United States Army Institute of Environmental Medicine, Natick, MA 01760, USA.
authors: Christopher T
authors: CT
authors: Carrigan
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors: Casey A
authors: CA
authors: Gifford
authors: Military Performance Division, United States Army Institute of Environmental Medicine, Natick, MA 01760, USA.
authors: Melissa A
authors: MA
authors: Kottke
authors: Department of Biological Chemistry and Molecular Pharmacology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Marcella
authors: M
authors: Cesana
authors: Lincoln Laboratory, Massachusetts Institute of Technology, Lexington, MA 02127, USA.
authors: Jackson
authors: J
authors: Lee
authors: Military Performance Division, United States Army Institute of Environmental Medicine, Natick, MA 01760, USA.
authors: Maria L
authors: ML
authors: Urso
authors: Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA.
authors: Alexander
authors: A
authors: Meissner
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D018482:Muscle, Skeletal / Q000293:injuries* / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D012038:Regeneration / Q000235:genetics*; D014158:Transcription, Genetic; D014945:Wound Healing / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger