2025-10-13 マックス・プランク研究所
Full muscle power only with TAF4A: If the transcription factor is active in muscle stem cells, the cell nuclei are intact (top left), while the absence of TAF4A results in unstable cell nuclei (top right). As a result, the regenerative capacity of muscles (bottom row) without TAF4A (right) is severely impaired. In comparison, the muscle cells in the tissue section of control animals with TAF4A appear regular and intact.
© MPI for Heart and Lung Research
<関連情報>
- https://www.mpg.de/25545861/how-muscle-stem-cells-maintain-regenerative-power
- https://www.nature.com/articles/s41467-025-64402-1
TAF4AによるNSLの制御は、ゲノムの安定性と筋幹細胞の静止に重要である Regulation of NSL by TAF4A is critical for genome stability and quiescence of muscle stem cells
Angelina M. Georgieva,Krishna Sreenivasan,Dong Ding,Clementine Villeneuve,Sara A. Wickström,Stefan Günther,Carsten Kuenne,Ulrich Gärtner,Xinyue Guo,Yonggang Zhou,Xuejun Yuan & Thomas Braun
Nature Communications Published:30 September 2025
DOI:https://doi.org/10.1038/s41467-025-64402-1
Abstract
Acetylation of lamin A/C by the non-specific lethal complex, containing MOF and KANSL2, is instrumental for maintaining nuclear architecture and genome stability, but the mechanisms controlling expression of its components in different cell types are poorly characterized. Here, we show that TAF4A, primarily known as a subunit of TFIID, forms a complex with the heterotrimeric transcription factor NF-Y and is critical for cell type-specific regulation of Kansl2 in muscle stem cells. Inactivation of Taf4a reduces expression of Kansl2 and alters post-translational modification of lamin A/C, thereby decreasing nuclear stiffness, which disrupts the nuclear architecture and results in severe genomic instability. Reduced expression of Kansl2 in Taf4a-mutant muscle stem cells changes expression of numerous genes involved in chromatin regulation. The subsequent loss of heterochromatin, in combination with pronounced genomic instability, activates muscle stem cells but impairs their proliferation, which depletes the stem cell pool and abolishes skeletal muscle regeneration. We conclude that TAF4A-NF-Y-dependent transcription regulation safeguards heterochromatin and genome stability of muscle stem cells via the non-specific lethal complex.
