Transcriptional coupling of telomeric retrotransposons with the cell cycle.

Unlike most species that use telomerase for telomere maintenance, many dipterans, including , rely on three telomere-specific retrotransposons (TRs)-, , and -to form tandem repeats at chromosome ends. Although TR transcription is crucial in their life cycle, its regulation remains poorly understood. This study identifies the Mediator complex, E2F1-Dp, and Scalloped/dTEAD as key regulators of TR transcription.

Distinct effects of CDK8 module subunits on cellular growth and proliferation in Drosophila.

The Mediator complex plays a pivotal role in facilitating RNA polymerase II-dependent transcription in eukaryotes. Within this complex, the CDK8 kinase module (CKM), comprising CDK8, Cyclin C (CycC), Med12 and Med13, serves as a dissociable subcomplex that modulates the activity of the small Mediator complex. Genetic studies in Drosophila have revealed distinct phenotypes associated with mutations in CKM subunits, but the underlying mechanisms have remained unclear.

Wnt/Wingless signaling promotes lipid mobilization through signal-induced transcriptional repression.

The Wnt/Wingless signaling pathway plays critical roles in metazoan development and energy metabolism, but its role in regulating lipid homeostasis remains not fully understood. Here, we report that the activation of canonical Wnt/Wg signaling promotes lipolysis while concurrently inhibiting lipogenesis and fatty acid β-oxidation in both larval and adult adipocytes, as well as cultured S2R+ cells, in . Using RNA-sequencing and CUT&RUN (Cleavage Under Targets & Release Using Nuclease) assays, we identified a set of Wnt target genes responsible for intracellular lipid homeostasis.

Metabolic control by the Bithorax Complex-Wnt signaling crosstalk in .

Adipocytes distributed throughout the body play crucial roles in lipid metabolism and energy homeostasis. Regional differences among adipocytes influence normal function and disease susceptibility, but the mechanisms driving this regional heterogeneity remain poorly understood. Here, we report a genetic crosstalk between the ( ) genes and Wnt/Wingless signaling that orchestrates regional differences among adipocytes in larvae.

Distinct effects of CDK8 module subunits on cellular growth and proliferation in .

Unlabelled: The Mediator complex, composed of about 30 conserved subunits, plays a pivotal role in facilitating RNA polymerase II-dependent transcription in eukaryotes. Within this complex, the CDK8 kinase module (CKM), comprising Med12, Med13, CDK8, and CycC (Cyclin C), serves as a dissociable subcomplex that modulates the activity of the small Mediator complex. Genetic studies in have revealed distinct phenotypes of CDK8-CycC and Med12-Med13 mutations, yet the underlying mechanism has remained unknown.

Transcriptional coupling of telomeric retrotransposons with the cell cycle.

Instead of employing telomerases to safeguard chromosome ends, dipteran species maintain their telomeres by transposition of telomeric-specific retrotransposons (TRs): in , these are , , and . Previous studies have shown how these TRs create tandem repeats at chromosome ends, but the exact mechanism controlling TR transcription has remained unclear. Here we report the identification of multiple subunits of the transcription cofactor Mediator complex and transcriptional factors Scalloped (Sd, the TEAD homolog in flies) and E2F1-Dp as novel regulators of TR transcription and telomere length in .

Cdk8 attenuates lipogenesis by inhibiting SREBP-dependent transcription in Drosophila.

Fine-tuning of lipogenic gene expression is important for the maintenance of long-term homeostasis of intracellular lipids. The SREBP family of transcription factors are master regulators that control the transcription of lipogenic and cholesterogenic genes, but the mechanisms modulating SREBP-dependent transcription are still not fully understood. We previously reported that CDK8, a subunit of the transcription co-factor Mediator complex, phosphorylates SREBP at a conserved threonine residue.

HP1c regulates development and gut homeostasis by suppressing Notch signaling through Su(H).

Notch signaling and epigenetic factors are known to play critical roles in regulating tissue homeostasis in most multicellular organisms, but how Notch signaling coordinates with epigenetic modulators to control differentiation remains poorly understood. Here, we identify heterochromatin protein 1c (HP1c) as an essential epigenetic regulator of gut homeostasis in Drosophila. Specifically, we observe that HP1c loss-of-function phenotypes resemble those observed after Notch signaling perturbation and that HP1c interacts genetically with components of the Notch pathway.

All-Atomic Molecular Dynamic Studies of Human and CDK8: Insights into Their Kinase Domains, the LXXLL Motifs, and Drug Binding Site.

Cyclin-dependent kinase 8 (CDK8) and its regulatory partner Cyclin C (CycC) play conserved roles in modulating RNA polymerase II (Pol II)-dependent gene expression. To understand the structure and function relations of CDK8, we analyzed the structures of human and CDK8 proteins using molecular dynamics simulations, combined with functional analyses in . Specifically, we evaluated the structural differences between hCDK8 and dCDK8 to predict the effects of the LXXLL motif mutation (AQKAA), the P154L mutations, and drug binding on local structures of the CDK8 proteins.

The Mediator CDK8-Cyclin C complex modulates Dpp signaling in Drosophila by stimulating Mad-dependent transcription.

Dysregulation of CDK8 (Cyclin-Dependent Kinase 8) and its regulatory partner CycC (Cyclin C), two subunits of the conserved Mediator (MED) complex, have been linked to diverse human diseases such as cancer. Thus, it is essential to understand the regulatory network modulating the CDK8-CycC complex in both normal development and tumorigenesis. To identify upstream regulators or downstream effectors of CDK8, we performed a dominant modifier genetic screen in Drosophila based on the defects in vein patterning caused by specific depletion or overexpression of CDK8 or CycC in developing wing imaginal discs.

Understanding Obesity as a Risk Factor for Uterine Tumors Using Drosophila.

Multiple large-scale epidemiological studies have identified obesity as an important risk factor for a variety of human cancers, particularly cancers of the uterus, gallbladder, kidney, liver, colon, and ovary, but there is much uncertainty regarding how obesity increases the cancer risks. Given that obesity has been consistently identified as a major risk factor for uterine tumors, the most common malignancies of the female reproductive system, we use uterine tumors as a pathological context to survey the relevant literature and propose a novel hypothesis: chronic downregulation of the cyclin-dependent kinase 8 (CDK8) module, composed of CDK8 (or its paralog CDK19), Cyclin C, MED12 (or MED12L), and MED13 (or MED13L), by elevated insulin or insulin-like growth factor signaling in obese women may increase the chances to dysregulate the activities of transcription factors regulated by the CDK8 module, thereby increasing the risk of uterine tumors. Although we focus on endometrial cancer and uterine leiomyomas (or fibroids), two major forms of uterine tumors, our model may offer additional insights into how obesity increases the risk of other types of cancers and diseases.

A conserved PLPLRT/SD motif of STING mediates the recruitment and activation of TBK1.

Nucleic acids from bacteria or viruses induce potent immune responses in infected cells. The detection of pathogen-derived nucleic acids is a central strategy by which the host senses infection and initiates protective immune responses. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor.

CDK8 mediates the dietary effects on developmental transition in Drosophila.

The complex interplay between genetic and environmental factors, such as diet and lifestyle, defines the initiation and progression of multifactorial diseases, including cancer, cardiovascular and metabolic diseases, and neurological disorders. Given that most of the studies have been performed in controlled experimental settings to ensure the consistency and reproducibility, the impacts of environmental factors, such as dietary perturbation, on the development of animals with different genotypes and the pathogenesis of these diseases remain poorly understood. By analyzing the cdk8 and cyclin C (cycC) mutant larvae in Drosophila, we have previously reported that the CDK8-CycC complex coordinately regulates lipogenesis by repressing dSREBP (sterol regulatory element-binding protein)-activated transcription and developmental timing by activating EcR (ecdysone receptor)-dependent gene expression.

An efficient and multiple target transgenic RNAi technique with low toxicity in Drosophila.

Being relatively simple and practical, Drosophila transgenic RNAi is the technique of top priority choice to quickly study genes with pleiotropic functions. However, drawbacks have emerged over time, such as high level of false positive and negative results. To overcome these shortcomings and increase efficiency, specificity and versatility, we develop a next generation transgenic RNAi system.

The Lysine Demethylase dKDM2 Is Non-essential for Viability, but Regulates Circadian Rhythms in .

Post-translational modification of histones, such as histone methylation controlled by specific methyltransferases and demethylases, play critical roles in modulating chromatin dynamics and transcription in eukaryotes. Misregulation of histone methylation can lead to aberrant gene expression, thereby contributing to abnormal development and diseases such as cancer. As such, the mammalian lysine-specific demethylase 2 (KDM2) homologs, KDM2A and KDM2B, are either oncogenic or tumor suppressive depending on specific pathological contexts.

The effect and biological mechanism of granular sludge size on performance of autotrophic nitrogen removal system.

The autotrophic process for nitrogen removal has attracted worldwide attention in the field of wastewater treatment, and the performance of this process is greatly influenced by the size of granular sludge particles present in the system. In this work, the granular sludge was divided into three groups, i.e.

Next-generation CRISPR/Cas9 transcriptional activation in using flySAM.

CRISPR/Cas9-based transcriptional activation (CRISPRa) has recently emerged as a powerful and scalable technique for systematic overexpression genetic analysis in We present flySAM, a potent tool for in vivo CRISPRa, which offers major improvements over existing strategies in terms of effectiveness, scalability, and ease of use. flySAM outperforms existing in vivo CRISPRa strategies and approximates phenotypes obtained using traditional Gal4-UAS overexpression. Moreover, because flySAM typically requires only a single sgRNA, it dramatically improves scalability.

Bidirectional and long-lasting control of alcohol-seeking behavior by corticostriatal LTP and LTD.

Addiction is proposed to arise from alterations in synaptic strength via mechanisms of long-term potentiation (LTP) and depression (LTD). However, the causality between these synaptic processes and addictive behaviors is difficult to demonstrate. Here we report that LTP and LTD induction altered operant alcohol self-administration, a motivated drug-seeking behavior.

Reversal of hyperactive Wnt signaling-dependent adipocyte defects by peptide boronic acids.

Deregulated Wnt signaling and altered lipid metabolism have been linked to obesity, diabetes, and various cancers, highlighting the importance of identifying inhibitors that can modulate Wnt signaling and aberrant lipid metabolism. We have established a model with hyperactivated Wnt signaling caused by partial loss of axin, a key component of the Wnt cascade. The mutant larvae are transparent and have severe adipocyte defects caused by up-regulation of β-catenin transcriptional activities.

Cyclic GMP-AMP Ameliorates Diet-induced Metabolic Dysregulation and Regulates Proinflammatory Responses Distinctly from STING Activation.

Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays any roles in regulating metabolic homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregulation and uniquely alters proinflammatory responses.

Structural basis for concerted recruitment and activation of IRF-3 by innate immune adaptor proteins.

Type I IFNs are key cytokines mediating innate antiviral immunity. cGMP-AMP synthase, ritinoic acid-inducible protein 1 (RIG-I)-like receptors, and Toll-like receptors recognize microbial double-stranded (ds)DNA, dsRNA, and LPS to induce the expression of type I IFNs. These signaling pathways converge at the recruitment and activation of the transcription factor IRF-3 (IFN regulatory factor 3).

Histone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation.

Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Histone H1 is one of the most critical chromatin regulators, but its role in adult stem cell regulation remains unclear. Here we report that H1 is intrinsically required in the regulation of germline stem cells (GSCs) in the Drosophila ovary.

Bioaugmentation of nitrate-dependent anaerobic ferrous oxidation by heterotrophic denitrifying sludge addition: A promising way for promotion of chemoautotrophic denitrification.

Nitrate-dependent anaerobic ferrous oxidation (NAFO) is a new and valuable bio-process for the treatment of wastewaters with low C/N ratio, and the NAFO process is in state of the art. The heterotrophic denitrifying sludge (HDS), possessing NAFO activity, was used as bioaugmentation to enhance NAFO efficiency. At a dosage of 6% (V/V), the removal of nitrate and ferrous was 2.

CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions through the Ecdysone Receptor in Drosophila.

The steroid hormone ecdysone and its receptor (EcR) play critical roles in orchestrating developmental transitions in arthropods. However, the mechanism by which EcR integrates nutritional and developmental cues to correctly activate transcription remains poorly understood. Here, we show that EcR-dependent transcription, and thus, developmental timing in Drosophila, is regulated by CDK8 and its regulatory partner Cyclin C (CycC), and the level of CDK8 is affected by nutrient availability.