THESIS
2016
vii, 41 pages : illustrations (some color) ; 30 cm
Abstract
Skeletal muscle satellite cells are responsible for postnatal skeletal muscle development
and regeneration and are kept in the quiescent state under normal condition in adult muscles.
Upon muscle injury, these cells become activated, proliferate and differentiate into new
myofibers while some satellite cells go back to quiescence to maintain the stem cell pool. In
skeletal muscles, Pax7 specifically marks the muscle satellite cells and is indispensable for their
maintenance and proliferation. Paxbp1 is a nuclear protein we recently identified that
specifically interacts with Pax7 and facilitates its recruitment of the H3K4 histone
methyltransferase (HMT) to promote satellite cell proliferation. Paxbp1 is also expressed in
proliferating myoblasts that have low or no Pax7 expressi...[
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Skeletal muscle satellite cells are responsible for postnatal skeletal muscle development
and regeneration and are kept in the quiescent state under normal condition in adult muscles.
Upon muscle injury, these cells become activated, proliferate and differentiate into new
myofibers while some satellite cells go back to quiescence to maintain the stem cell pool. In
skeletal muscles, Pax7 specifically marks the muscle satellite cells and is indispensable for their
maintenance and proliferation. Paxbp1 is a nuclear protein we recently identified that
specifically interacts with Pax7 and facilitates its recruitment of the H3K4 histone
methyltransferase (HMT) to promote satellite cell proliferation. Paxbp1 is also expressed in
proliferating myoblasts that have low or no Pax7 expression, suggesting that it also has Pax7-independent functions. In particular, its function in myoblast differentiation remains unclear.
Knockdown of Paxbp1 inhibits the differentiation of primary myoblasts and C2C12 myogenic
cell line. Furthermore, our previous work revealed that Paxbp1 promotes the transcriptional
activity of Myf5 by bridging Myf5 and Brg1, a core catalytic subunit of the SWI/SNF chromatin
remodeling complex. To study the function of Paxbp1 in satellite cells in vivo, we generated a
line of inducible satellite cell-specific Paxbp1 knockout mice. Following Paxbp1 deletion in
adult muscle satellite cells induced by continuous tamoxifen treatment, muscle regeneration
was greatly impaired. Satellite cells exhibited severe deficiency in proliferation and
differentiation. Therefore, we demonstrated that Paxbp1 is crucial for satellite cell normal
function and skeletal regeneration in vivo. Meanwhile, to better understand the molecular
mechanism of the functions of Paxbp1 in muscle satellite cells and skeletal muscle regeneration,
we plan to screen for other Paxbp1 binding targets by BioID assays. Such efforts should help
us better understand the functions of Paxbp1 in muscle satellite cells.
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