The Super Elongation Complex (SEC) in Development and Disease

Chromosomal translocations involving the mixed lineage leukemia (MLL) gene are associated with infant acute leukemia. There are a large number of translocation partners of MLL that share very little sequence similarities, yet their translocations into MLL result in the pathogenesis of leukemia. To define the molecular reason why these translocations result in leukemogenesis, I purified several of the commonly occurring MLL chimeras and identified a novel Super Elongation Complex (SEC) associated with all chimeras purified. SEC consists of the RNA Pol II elongation factors ELL1-3, P-TEFb, and several frequent MLL-translocation partners. SEC is one of the most active P-TEFb complexes and is required for the proper expression of MLL chimera target genes and the oncogene, MYC, suggesting that the regulation of transcription elongation checkpoint control (TECC) by SEC could play essential roles in leukemia. Paused Pol II has been proposed to be associated with loci that respond rapidly to environmental stimuli. My studies in mouse ES cells demonstrated that SEC is required for rapid transcriptional activation of genes, many of which contain paused Pol II. However, SEC is also required for the activation of the Cyp26al gene, which does not contain detectable Pol II, yet responds much more rapidly to retinoic acid than those paused genes, suggesting that paused Pol II is not a prerequisite for rapid gene activation. Furthermore, Ell3, a member of the ELL family of proteins, predominately occupies poised, active, and inactive enhancers of many developmental genes in ES cells. Ell3’s association with enhancers is required for setting up proper Pol II occupancy at the promoter-proximal regions of neighboring genes, providing a yet to be discovered mechanism for the transition from Ell3’s presence at poised enhancers in ES cells to Ell2’s role in the release of paused Pol II during gene activation

Comparative Analyses of H3K4 and H3K27 Trimethylations Between the Mouse Cerebrum and Testis

AbstractThe global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. However, the bivalent domains tend towards a “winner-takes-all” approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a “winner-takes-all” principle to regulate gene expression

Large-scale collection and annotation of gene models for date palm (Phoenix dactylifera, L.)

The date palm (Phoenix dactylifera L.), famed for its sugar-rich fruits (dates) and cultivated by humans since 4,000 B.C., is an economically important crop in the Middle East, Northern Africa, and increasingly other places where climates are suitable. Despite a long history of human cultivation, the understanding of P. dactylifera genetics and molecular biology are rather limited, hindered by lack of basic data in high quality from genomics and transcriptomics. Here we report a large-scale effort in generating gene models (assembled expressed sequence tags or ESTs and mapped to a genome assembly) for P. dactylifera, using the long-read pyrosequencing platform (Roche/454 GS FLX Titanium) in high coverage. We built fourteen cDNA libraries from different P. dactylifera tissues (cultivar Khalas) and acquired 15,778,993 raw sequencing reads—about one million sequencing reads per library—and the pooled sequences were assembled into 67,651 non-redundant contigs and 301,978 singletons. We annotated 52,725 contigs based on the plant databases and 45 contigs based on functional domains referencing to the Pfam database. From the annotated contigs, we assigned GO (Gene Ontology) terms to 36,086 contigs and KEGG pathways to 7,032 contigs. Our comparative analysis showed that 70.6 % (47,930), 69.4 % (47,089), 68.4 % (46,441), and 69.3 % (47,048) of the P. dactylifera gene models are shared with rice, sorghum, Arabidopsis, and grapevine, respectively. We also assigned our gene models into house-keeping and tissue-specific genes based on their tissue specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11103-012-9924-z) contains supplementary material, which is available to authorized users

Human Mediator Subunit MED26 Functions as a Docking Site for Transcription Elongation Factors

SummaryPromoter-proximal pausing by initiated RNA polymerase II (Pol II) and regulated release of paused polymerase into productive elongation has emerged as a major mechanism of transcription activation. Reactivation of paused Pol II correlates with recruitment of super-elongation complexes (SECs) containing ELL/EAF family members, P-TEFb, and other proteins, but the mechanism of their recruitment is an unanswered question. Here, we present evidence for a role of human Mediator subunit MED26 in this process. We identify in the conserved N-terminal domain of MED26 overlapping docking sites for SEC and a second ELL/EAF-containing complex, as well as general initiation factor TFIID. In addition, we present evidence consistent with the model that MED26 can function as a molecular switch that interacts first with TFIID in the Pol II initiation complex and then exchanges TFIID for complexes containing ELL/EAF and P-TEFb to facilitate transition of Pol II into the elongation stage of transcription

The Disequilibrium of Nucleosomes Distribution along Chromosomes Plays a Functional and Evolutionarily Role in Regulating Gene Expression

To further understand the relationship between nucleosome-space occupancy (NO) and global transcriptional activity in mammals, we acquired a set of genome-wide nucleosome distribution and transcriptome data from the mouse cerebrum and testis based on ChIP (H3)-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues—cerebrum, testis, and ESCs—and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes are closely associated with distinct expression levels between house-keeping (HK) genes and tissue-specific (TS) genes. Both TS and HK genes form clusters albeit the obvious majority. This feature implies that NO patterns, i.e. nucleosome binding and clustering, are coupled with gene clustering that may be functionally and evolutionarily conserved in regulating gene expression among different cell types

The IPIN 2019 Indoor Localisation Competition—Description and Results

IPIN 2019 Competition, sixth in a series of IPIN competitions, was held at the CNR Research Area of Pisa (IT), integrated into the program of the IPIN 2019 Conference. It included two on-site real-time Tracks and three off-site Tracks. The four Tracks presented in this paper were set in the same environment, made of two buildings close together for a total usable area of 1000 m 2 outdoors and and 6000 m 2 indoors over three floors, with a total path length exceeding 500 m. IPIN competitions, based on the EvAAL framework, have aimed at comparing the accuracy performance of personal positioning systems in fair and realistic conditions: past editions of the competition were carried in big conference settings, university campuses and a shopping mall. Positioning accuracy is computed while the person carrying the system under test walks at normal walking speed, uses lifts and goes up and down stairs or briefly stops at given points. Results presented here are a showcase of state-of-the-art systems tested side by side in real-world settings as part of the on-site real-time competition Tracks. Results for off-site Tracks allow a detailed and reproducible comparison of the most recent positioning and tracking algorithms in the same environment as the on-site Tracks

The Effect of Kinesiology Taping on the Hemiplegic Shoulder Pain: A Randomized Controlled Trial

Objective. The purpose of the study was to explore the effect of kinesiology taping on hemiplegic shoulder pain (HSP) in terms of pain intensity, magnitude of subluxation, muscle activity, and active range of motion (AROM). Design. Double-blind, placebo-controlled clinical trial. Setting. the Rehabilitation Center of the West China Hospital. Participants. Nineteen individuals suffering from HSP were recruited in this study. Intervention. Patients were randomly assigned into the taping group or control group. The taping group received therapeutic kinesiology taping and conventional treatment, while the control group received placebo taping (applied without tension) and conventional treatment. Main Outcome Measures. The shoulder pain intensity (numerical pain rating scale), magnitude of subluxation, muscle activity (measured by surface electromyography (sEMG)), and shoulder active range of movement (AROM) were assessed at the baseline, on the first day (immediately after taping) and 4 weeks after treatment (without taping). Results. All patients completed the trials. There were no significant differences between groups at the baseline. The taping group showed immediate improvement on the first day after taping in terms of pain intensity, magnitude of subluxation, and muscle activity (p0.05). After 4 weeks of treatment, the taping group showed significant changes in pain intensity, magnitude of subluxation, muscle activity, and AROM (p<0.05). And significant differences in pain intensity and muscle activity could be seen between the two groups (p<0.05). Conclusion. The results indicate that the kinesiology taping is effective in reducing the shoulder pain and subluxation and increasing muscle activity and AROM for patients with HSP after stroke

The super elongation complex (SEC) and MLL in development and disease

Transcriptional regulation at the level of elongation is vital for the control of gene expression and metazoan development. The mixed lineage leukemia (MLL) protein and its Drosophila homolog, Trithorax, which exist within COMPASS (complex of proteins associated with Set1)-like complexes, are master regulators of development. They are required for proper homeotic gene expression, in part through methylation of histone H3 on Lys 4. In humans, the MLL gene is involved in a large number of chromosomal translocations that create chimeric proteins, fusing the N terminus of MLL to several proteins that share little sequence similarity. Several frequent translocation partners of MLL were found recently to coexist in a super elongation complex (SEC) that includes known transcription elongation factors such as eleven-nineteen lysine-rich leukemia (ELL) and P-TEFb. Importantly, the SEC is required for HOX gene expression in leukemic cells, suggesting that chromosomal translocations involving MLL could lead to the overexpression of HOX and other genes through the involvement of the SEC. Here, we review the normal developmental roles of MLL and the SEC, and how MLL fusion proteins can mediate leukemogenesis