The induction of proinflammatory proteins in stimulated endothelial cells (EC) requires activation of multiple transcription programs. The homeobox transcription factor HOXA9 has an important regulatory role in cytokine induction of the EC-leukocyte adhesion molecules (ELAM) E-selectin and vascular cell adhesion molecule 1 (VCAM-1). However, the mechanism underlying stimulus-dependent activation of HOXA9 is completely unknown. Here, we elucidate the molecular mechanism of HOXA9 activation by tumor necrosis factor alpha (TNF-␣) and show an unexpected requirement for arginine methylation by protein arginine methyltransferase 5 (PRMT5). PRMT5 was identified as a TNF-␣-dependent binding partner of HOXA9 by mass spectrometry. Small interfering RNA (siRNA)-mediated depletion of PRMT5 abrogated stimulus-dependent HOXA9 methylation with concomitant loss in E-selectin or VCAM-1 induction. Chromatin immunoprecipitation analysis revealed that PRMT5 is recruited to the E-selectin promoter following transient HOXA9 binding to its cognate recognition sequence. PRMT5 induces symmetric dimethylation of Arg140 on HOXA9, an event essential for E-selectin induction. In summary, PRMT5 is a critical coactivator component in a newly defined, HOXA9-containing transcription complex. Moreover, stimulus-dependent methylation of HOXA9 is essential for ELAM expression during the EC inflammatory response.

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The Achilles tendon is a common site of anatomical injury among athletes and those participating in recreational sporting activities. Acute Achilles tendon ruptures are often misdiagnosed as a sprained ankle and are more common in the male population. Mechanism of injury is often a noncontact injury, resulting from sudden forced plantar flexion or violent dorsiflexion in a plantar flexed foot. Delays in diagnosis and treatment may complicate the clinical outcome. Because findings may be subtle on history and physical examination, the use of readily available adjunctive studies is important for practitioners. One method is the analysis of Kager's triangle on lateral ankle radiographs. Obscuration of Kager's triangle has been described as a radiographic indicator of Achilles tendon rupture, but the sensitivity and specificity of this finding have been poorly reported. [ Orthopedics . 2020; 43(2): e91–e94.]