The Role of the Set1 RNA Polymerase II Interacting Motif (SRIM) in Set1 Recruitment and Histone H3K4 Methylation

In eukaryotes, gene expression is regulated by epigenetic modifications. Among these modifications, histone H3 lysine 4 (H3K4) methylation has been associated with transcription activation. Set1 is the sole H3K4 histone methyltransferase in Saccharomyces cerevisiae and functions in a multi-subunit protein complex (Set1C) to catalyze H3K4 mono-, di-, and trimethylation. In addition, mis-regulation of Set1 human orthologs such as MLL (1 to 4) or SETD1A/B have been linked to a variety of cancers such as leukemia and early embryonic development defects. The current model indicates that the Paf1 complex (RNA polymerase II associated factor I) recruits Set1C to the phosphorylated CTD of RNA polymerase II (RNAPII) and chromatin, so that Set1C can deposit histone H3K4 methylation at actively transcribed genes. Here we show that the Set1 and RNAPII association is independent of Paf1 complex subunits. Our results also show that Set1 and RNAPII can interact independently of Set1-associated subunits. We have identified, for the first time, the region responsible for the Set1 and RNAPII interaction and have named this region the Set1 RNA polymerase II interacting motif (SRIM), which is in the uncharacterized region upstream of the previously identified Set1 RNA Recognition Motifs (RRM). Importantly, we have determined that Set1 interacts with the Ser5 phosphorylated form of CTD and that the SRIM is necessary for this interaction. Additionally, SRIM mutants show altered enrichment at mostly the 5’ regions of open reading frames of actively transcribed genes, including PYK1 and PMA1 and inducible genes, including PCK1. Moreover, one SRIM mutant shows a great decrease in H3K4 trimethylation levels globally and gene specifically. Interestingly, the deposition of global H3K4 mono- and dimethylation still occurs in the SRIM mutants. Together, these results suggest that the Set1 and RNAPII interaction is important for proper recruitment of Set1 and the deposition of H3K4 trimethylation to 5’ ends of actively transcribed genes, whereas Set1 could also be recruited to chromatin through other mechanisms independent of the Set1-RNAPII interaction to deposit H3K4 methylation. Furthermore, the loss of Set1 and SRIM mutants show sensitivity to 6-azauracil (6AU) indicating that the Set1 and RNAPII interaction is important for transcriptional elongation. Taken together, these data indicate that Set1 specifically interacts with the Ser5 phosphorylated form of RNAPII through the newly identified SRIM and that this interaction plays a role in the establishment of Set1-mediated H3K4 methylation to actively transcribing genes and inducible genes

The effects of primary olfactory cortical and thalamic lesions on olfactory continuous non-matching to sample and discrimination in the rat

Forty-two male rats were pretrained on the olfactory continuous delayed non-matching to sample (CDNMTS) task. They were then matched for performance and randomly assigned to one of the following six treatment groups: excitotoxic lesions of pyriform cortex, later entorhinal cortex, lateral internal medullary lamina (L-IML), mediodorsal nucleus (MDn), nonspecific nuclei, and sham control. After recovery from surgery, the rats were retrained on the olfactory CDNMTS. Delay effects were examined by manipulating retention intervals (RI), with five RIs (4, 6, 9, 13.5, and 20.25 s) randomly mixed within each session. The number of odor stimuli used in each session varied from 8 to 2. All the rats were then trained on olfactory discrimination task, a task with similar procedural requirements as olfactory CDNMTS except that the stimulus-response contingency was fixed. Only L-IML and pyriform groups were impaired on the olfactory CDNMTS. Increasing RIs or reducing number of odor stimuli used in each session significantly decreased performance accuracy for all the rats. There was no differential effects. All subjects learned the two-odor discrimination task at equivalent rates. The normal performance of discrimination task, indicated that the olfactory CDNMTS deficits could not be attributed to olfactory sensory dysfunction, to difficulties in learning the procedural aspects of the task, or to an inability to suppress responding. The present findings demonstrate that excitotoxic lesions of L-IML disrupt olfactory working memory but not reference memory, which is consistent with previous studies of radiofrequency lesions of L-IML. Pyriform cortex, a major primary olfactory cortex, apparently is not necessary for olfactory discrimination, although it is critical for olfactory CDNMTS. Taken together, it suggests that either pyriform cortex alone is critical for olfactory memory or there exist parallel pathways for olfactory memory processing

Stable and scalable congestion control for high-speed heterogeneous networks

For any congestion control mechanisms, the most fundamental design objectives are stability and scalability. However, achieving both properties are very challenging in such a heterogeneous environment as the Internet. From the end-users' perspective, heterogeneity is due to the fact that different flows have different routing paths and therefore different communication delays, which can significantly affect stability of the entire system. In this work, we successfully address this problem by first proving a sufficient and necessary condition for a system to be stable under arbitrary delay. Utilizing this result, we design a series of practical congestion control protocols (MKC and JetMax) that achieve stability regardless of delay as well as many additional appealing properties. From the routers' perspective, the system is heterogeneous because the incoming traffic is a mixture of short- and long-lived, TCP and non-TCP flows. This imposes a severe challenge on traditional buffer sizing mechanisms, which are derived using the simplistic model of a single or multiple synchronized long-lived TCP flows. To overcome this problem, we take a control-theoretic approach and design a new intelligent buffer sizing scheme called Adaptive Buffer Sizing (ABS), which based on the current incoming traffic, dynamically sets the optimal buffer size under the target performance constraints. Our extensive simulation results demonstrate that ABS exhibits quick responses to changes of traffic load, scalability to a large number of incoming flows, and robustness to generic Internet traffic

Enhancement of nitrate removal at the sediment-water interface by carbon addition plus vertical mixing

Author Posting. © The Author(s), 2014. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Chemosphere 136 (2015): 305-310, doi:10.1016/j.chemosphere.2014.12.010.Wetlands and ponds are frequently used to remove nitrate from effluents or runoffs. However, the efficiency of this approach is limited. Based on the assumption that introducing vertical mixing to water column plus carbon addition would benefit the diffusion across the sediment–water interface, we conducted simulation experiments to identify a method for enhancing nitrate removal. The results suggested that the sediment-water interface has a great potential for nitrate removal, and the potential can be activated after several days of acclimation. Adding additional carbon plus mixing significantly increases the nitrate removal capacity, and the removal of total nitrogen (TN) and nitrate-nitrogen (NO3--N) is well fitted to a first-order reaction model. Adding Hydrilla verticillata debris as a carbon source increased nitrate removal, whereas adding Eichhornia crassipe decreased it. Adding ethanol plus mixing greatly improved the removal performance, with the removal rate of NO3--N and TN reaching 15.0-16.5 g m-2 d-1. The feasibility of this enhancement method was further confirmed with a wetland microcosm, and the NO3--N removal rate maintained at 10.0-12.0 g m-2 d-1 at a hydraulic loading rate of 0.5 m d-1.The present work was supported by the State Oceanic Administration of China (Demonstration project of coastal wetland restoration, north coast of Hangzhou Wan bay), the National Science Foundation of China under Grant No. 51378306 and 41471393, and Science and Technology Planning Project of Zhejiang Province No.2014F50003