JARID2 is a direct target of the PAX3-FOXO1 fusion protein and inhibits myogenic differentiation of rhabdomyosarcoma cells

Rhabdomyosarcomas (RMS) are the most frequent soft-tissue sarcoma in children and characteristically show features of developing skeletal muscle. The alveolar subtype is frequently associated with a PAX3-FOXO1 fusion protein that is known to contribute to the undifferentiated myogenic phenotype of RMS cells. Histone methylation of lysine residues controls developmental processes in both normal and malignant cell contexts. Here we show that JARID2, that encodes a protein known to recruit various complexes with histone methylating activity to their target genes, is significantly overexpressed in RMS with PAX3-FOXO1 compared to fusion gene negative RMS (t test p<0.0001). Multivariate analyses showed higher JARID2 levels are also associated with metastases at diagnosis, independent of fusion gene status and RMS subtype (n= 120; p=0.039). JARID2 levels were altered by silencing or over-expressing PAX3-FOXO1 in RMS cell lines with and without the fusion gene, respectively. Consistent with this, we demonstrated that JARID2 is a direct transcriptional target of the PAX3-FOXO1 fusion protein. Silencing JARID2 resulted in reduced cell proliferation coupled with myogenic differentiation including increased expression of MYOGENIN (MYOG) and MYOSIN LIGHT CHAIN (MYL1) in RMS cell lines representative of both the alveolar and embryonal subtypes. Induced myogenic differentiation was associated with a decrease in JARID2 levels and this phenotype could be rescued by overexpressing JARID2. Furthermore, we that showed JARID2 binds to and alters the methylation status of histone H3 lysine 27 in the promoter regions of MYOG and MYL1 and that the interaction of JARID2 at these promoters is dependent upon EED, a core component of the Polycomb Repressive Complex 2 (PRC2). Therefore JARID2 is a downstream effector of PAX3-FOXO1 that maintains an undifferentiated myogenic phenotype that is characteristic of RMS. JARID2 and other components of PRC2 may represent novel therapeutic targets for treating RMS patients

Bacillus subtilis improves maize tolerance to salinity

ABSTRACT: The aim of this study was to evaluate the biochemical responses of maize, under saline stress, inoculated with Bacillus subtilis. Four levels of salinity were assessed: 0mM, 50mM, 100mM, and 200mM of sodium chloride (NaCl). Saline conditions influenced negatively maize growth. However, the inoculation of B. subtilis improved the plant growth at highest level of NaCl. Chlorophyll content decreased while proline increased in inoculated plants submitted to highest salt levels. Also, B. subtilis increased the relative water content in leaves. B. subtilis improves the plant growth under salinity and ameliorates the biochemical damages in maize

Bacillus subtilis improves maize tolerance to salinity

<div><p>ABSTRACT: The aim of this study was to evaluate the biochemical responses of maize, under saline stress, inoculated with Bacillus subtilis. Four levels of salinity were assessed: 0mM, 50mM, 100mM, and 200mM of sodium chloride (NaCl). Saline conditions influenced negatively maize growth. However, the inoculation of B. subtilis improved the plant growth at highest level of NaCl. Chlorophyll content decreased while proline increased in inoculated plants submitted to highest salt levels. Also, B. subtilis increased the relative water content in leaves. B. subtilis improves the plant growth under salinity and ameliorates the biochemical damages in maize.</p></div

CKIP-1 regulates mammalian and zebrafish myoblast fusion

Multinucleated muscle fibres arise by fusion of precursor cells called myoblasts. We previously showed that CKIP-1 ectopic expression in C2C12 myoblasts increased cell fusion. In this work, we report that CKIP-1 depletion drastically impairs C2C12 myoblast fusion in vitro and in vivo during zebrafish muscle development. Within developing fast-twich myotome, Ckip-1 localises at the periphery of fast precursor cells, closed to the plasma membrane. Unlike wild-type myoblasts that form spatially arrayed multinucleated fast myofibres, Ckip-1-deficient myoblasts show a drastic reduction in fusion capacity. A search for CKIP-1 binding partners identified the ARPC1 subunit of Arp2/3 actin nucleation complex essential for myoblast fusion. We demonstrate that CKIP-1, through binding to plasma membrane phosphoinositides via its PH domain, regulates cell morphology and lamellipodia formation by recruiting the Arp2/3 complex at the plasma membrane. These results establish CKIP-1 as a regulator of cortical actin that recruits the Arp2/3 complex at the plasma membrane essential for muscle precursor elongation and fusion

P/CAF mediates PAX3–FOXO1-dependent oncogenesis in alveolar rhabdomyosarcoma

10.1002/path.4773The Journal of Pathology2403269-28