Drosophila Argonaute2 (AGO2) has been shown to regulate expression of certain loci in an RNA interference (RNAi)-independent manner, but its genome-wide function on chromatin remains unknown. Here, we identified the nuclear scaffolding protein LaminB as a novel interactor of AGO2. When either AGO2 or LaminB are depleted in Kc cells, similar transcription changes are observed genome-wide. In par...

One of the transcription-independent mechanisms of the tumor suppressor p53 discovered in recent years involves physical interaction between p53 and proteins of the Bcl-2 family. In this paper, significant differences between the interaction of p53 with Mcl-1 and Bcl-xL were demonstrated by NMR spectroscopy and isothermal titration calorimetry. Bcl-xL was found to bind strongly to the p53 DNA-b...

The C-terminal activation domain (C-TAD) of the hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha binds the CH1 domains of the related transcriptional coactivators CREB-binding protein (CBP) and p300, an oxygen-regulated interaction thought to be highly essential for hypoxia-responsive transcription. The role of the CH1 domain in vivo is unknown, however. We created mutant mice ...

During recent years, there has been interest in once-a-day (OAD) milking. A comparison was made of OAD with twice-a-day (TAD) milking on a case study farm in northern Victoria. The comparison suggests that operating profit and internal rate of return are similar to TAD milking if the decrease in milk protein plus fat production, as a result of OAD milking, is less than 12 percent. Although a de...

OBJECTIVE The aim of this study was to evaluate whether intertrochanteric femur fractures can be reduced and nailed properly in the lateral decubitus position using Proximal Femoral Nail Antirotation (PFNA) as a fixation device without the use of a traction table. METHODS The study included 207 patients (81 male and 126 female; mean age: 75 years, range: 22 to 95 years). According to the Evan...

We have simulated the isomerization of 38-atom Lennard-Jones clusters (LJ38) – a well-known prototype system for global-optimization and energy landscape analyses – over a wide range of temperatures using a combination of molecular dynamics (MD) and temperature accelerated dynamics (TAD). At high temperatures, we find that (surprisingly) MD with steepest descent quenches (MDSDQ) is effective fo...

Higher order chromatin structure establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene provides a paradigm for investigating these mechanisms.CFTR occupies a TAD borde...

Gene regulation by cytokine-activated transcription factors of the signal transducer and activator of transcription (STAT) family requires serine phosphorylation within the transactivation domain (TAD). STAT1 and STAT3 TAD phosphorylation occurs upon promoter binding by an unknown kinase. Here, we show that the cyclin-dependent kinase 8 (CDK8) module of the Mediator complex phosphorylated regul...

The spatial arrangement of interphase chromosomes in the nucleus is important for gene expression and genome function in animals and in plants. The recently developed Hi-C technology is an efficacious method to investigate genome packing. Here we present a detailed Hi-C map of the three-dimensional genome organization of the plant Arabidopsis thaliana. We find that local chromatin packing diffe...

Metazoan genomes are organized into regions of topologically associating domains (TADs). TADs are demarcated by border elements, which are enriched for active genes and high occupancy architectural protein binding sites. We recently demonstrated that 3D chromatin architecture is dynamic in response to heat shock, a physiological stress that downregulates transcription and causes a global redist...