Genome-wide gene expression studies have indicated that the eukaryotic genome contains many gene pairs showing overlapping sense and antisense transcription. Regulation of these coding and/or noncoding gene pairs involves intricate regulatory mechanisms. In the present study, we utilized an enhanced green fluorescent protein (EGFP)-tagged reporter plasmid cis linked to a doxycycline-inducible antisense promoter, generating antisense transcription that fully overlaps EGFP, to study the mechanism and dynamics of gene silencing after induction of noncoding antisense transcription in undifferentiated and differentiating mouse embryonic stem cells (ESCs). We found that EGFP silencing is reversible in ESCs but is locked into a stable state upon ESC differentiation. Reversible silencing in ESCs is chromatin dependent and is associated with accumulation of trimethylated lysine 36 on histone H3 (H3K36me3) at the EGFP promoter region. In differentiating ESCs, antisense transcription-induced accumulation of H3K36me3 was associated with an increase in CpG methylation at the EGFP promoter. Repression of the sense promoter was affected by small-molecule inhibitors which interfere with DNA methylation and histone demethylation pathways. Our results indicate a general mechanism for silencing of fully overlapping sense-antisense gene pairs involving antisense transcription-induced accumulation of H3K36me3 at the sense promoter, resulting in reversible silencing of the sense partner, which is stabilized during ESC differentiation by CpG methylation.
The practical matters associated with management of blood-exposure incidents, such as timely reporting and administration of prophylaxis, should be optimized for incidents that occur at times other than regular office hours and outside of hospitals. The establishment of a 24-hour centralized counseling facility that was open 7 days a week to manage blood exposures resulted in significant improvements in incident management and better care.
8576 Background: Palliative sedation (PS) may be needed in dying cancer patients to achieve acceptable symptom control. Little is known about the differences between sedated and non-sedated patients. To determine characteristics of sedated and non-sedated patients, we performed a retrospective study in patients who died during admission to the palliative care unit (PCU) of the cancer center. Methods: From October 2001 until October 2005, 157 out of 753 admitted patients died at the PCU. The medical and nursing records were studied with respect to patient characteristics and the symptom profile at admission and during the last 72 hrs of life. Results: Of all deceased patients, 68 (43%) were sedated prior to death. The median duration of the sedation was 19 hrs (range 0.7–125). No differences between sedated and non-sedated patients were found in age (median 58 years, range 25–89) and time between admission and death (7 days, 1–38). The primary tumor sites were mostly lung (22.1%), GI tract (20.6%), and breast (16.2%) in the sedated patients, and breast (24.7%), lung (13.5%) and urogenital tract (11.2%) in the non-sedated patients. The symptoms at admission were mainly pain (82%), constipation (43%) and dyspnea (31%) and did not differ between both groups. Prior to the start of PS, sedated patients more often had delirium and dyspnea as compared to non-sedated patients at similar times before death. Conclusions: PS was needed to control symptoms for somewhat less than half of the patients dying at the PCU. Pain was a main reason for admission in both groups, but dyspnea and delirium were more common in sedated patients during admission. [Table: see text] No significant financial relationships to disclose.
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