RT Journal Article SR Electronic T1 Enhancer of Zeste Homolog 2 (Ezh2) is essential for patterning of multiple musculoskeletal tissues but dispensable for tendon differentiation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.10.30.361949 DO 10.1101/2020.10.30.361949 A1 Deepanwita Pal A1 Scott M. Riester A1 Bashar Hasan A1 Sara F. Tufa A1 Amel Dudakovic A1 Douglas R. Keene A1 Andre J. van Wijnen A1 Ronen Schweitzer YR 2020 UL http://biorxiv.org/content/early/2020/10/30/2020.10.30.361949.abstract AB An efficient musculoskeletal system depends on the precise assembly and coordinated growth and function of muscles, skeleton and tendons. However, the mechanisms that drive integrated musculoskeletal development and coordinated growth and differentiation of each of these tissues are still being uncovered. Epigenetic modifiers have emerged as critical regulators of cell fate differentiation, but so far almost nothing is known about their roles in tendon biology. Previous studies have shown that epigenetic modifications driven by Enhancer of zeste homolog 2 (EZH2), a major histone methyltransferase, have significant roles in vertebrate development including skeletal patterning and bone formation. We now find that targeting Ezh2 through the limb mesenchyme also has significant effects on tendon and muscle patterning, likely reflecting the essential roles of early mesenchymal cues mediated by Ezh2 for coordinated patterning and development of all tissues of the musculoskeletal system. Conversely, loss of Ezh2 in the tendon cells did not disrupt the tendon cell fate suggesting that tenocyte differentiation and tendon maturation are independent of Ezh2 signaling.