Dynamic sumoylation of promoter-bound general transcription factors facilitates transcription by RNA polymerase II.

Transcription-related proteins are frequently identified as targets of sumoylation, including multiple subunits of the RNA polymerase II (RNAPII) general transcription factors (GTFs). However, it is not known how sumoylation affects GTFs or whether they are sumoylated when they assemble at promoters to facilitate RNAPII recruitment and transcription initiation. To explore how sumoylation can regulate transcription genome-wide, we performed SUMO ChIP-seq in yeast and found, in agreement with others, that most chromatin-associated sumoylated proteins are detected at genes encoding tRNAs and ribosomal proteins (RPGs). However, we also detected 147 robust SUMO peaks at promoters of non-ribosomal protein-coding genes (non-RPGs), indicating that sumoylation also regulates this gene class. Importantly, SUMO peaks at non-RPGs align specifically with binding sites of GTFs, but not other promoter-associated proteins, indicating that it is GTFs specifically that are sumoylated there. Predominantly, non-RPGs with SUMO peaks are among the most highly transcribed, have high levels of TFIIF, and show reduced RNAPII levels when cellular sumoylation is impaired, linking sumoylation with elevated transcription. However, detection of promoter-associated SUMO by ChIP might be limited to sites with high levels of substrate GTFs, and promoter-associated sumoylation at non-RPGs may actually be far more widespread than we detected. Among GTFs, we found that TFIIF is a major target of sumoylation, specifically at lysines 60/61 of its Tfg1 subunit, and elevating Tfg1 sumoylation resulted in decreased interaction of TFIIF with RNAPII. Interestingly, both reducing promoter-associated sumoylation, in a sumoylation-deficient Tfg1-K60/61R mutant strain, and elevating promoter-associated SUMO levels, by constitutively tethering SUMO to Tfg1, resulted in reduced RNAPII occupancy at non-RPGs. This implies that dynamic GTF sumoylation at non-RPG promoters, not simply the presence or absence of SUMO, is important for maintaining elevated transcription. Together, our findings reveal a novel mechanism of regulating the basal transcription machinery through sumoylation of promoter-bound GTFs.

Short- and long-term continuous positive airway pressure usage in the post-stroke population with obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) is highly prevalent in post-stroke patients and observational evidence suggests that untreated it is a harbinger of poorer outcomes in this population. Clinical trials on the impact of treatment of OSA with continuous positive airway pressure (CPAP) have countered difficulties with patient engagement and adherence to CPAP therapy. Real-world data on continuous positive airway pressure initiation and usage in the post-stroke population with obstructive sleep apnea is limited. METHODS: We performed a clinical retrospective study between January 2006 and June 2015 to describe the short- and long-term CPAP usage in the post-stroke population with OSA, and to assess which patient, disease, and treatment-related factors were associated with CPAP purchase, initiation, and usage in this population. RESULTS: Of 191 post-stroke patients' recommended CPAP therapy, post-prescription usage at 3, 6, 12, 24, and 60 months was 58%, 53%, 48%, 45%, and 39% respectively. OSA severity-related factors, such as AHI or degree of nocturnal hypoxemia, were not significantly associated with CPAP usage. Predictors of CPAP usage at all time points were younger age, male sex, never smokers, and no history of hypertension. There were some differences in predictors of CPAP usage between early and later time periods. CONCLUSIONS: We demonstrated that the long-term usage of CPAP therapy is possible with most of the attrition occurring in the first 3 months. Upfront healthcare resource allocation to CPAP initiation and usage in this population may improve longer-term usage.