A genetic screen supports a broad role for the Drosophila insulator proteins BEAF-32A and BEAF-32B in maintaining patterns of gene expression. | LitMetric
Chromatin domain insulators are thought to insulate adjacent genes, including their regulatory elements, from each other by organizing chromatin into functionally independent domains. Thus insulators should play a global role in gene regulation by keeping regulatory domains separated. However, this has never been demonstrated. We previously designed and characterized a transgene that is under GAL4 UAS control and encodes a dominant-negative form of the Boundary Element-Associated Factors BEAF-32A and BEAF-32B. The BID transgene encodes the BEAF self-interaction domain but lacks a DNA binding domain. Expression of BID in eye imaginal discs leads to a rough eye phenotype. Here we screen for dominant mutations that modify this eye phenotype. This assay provides evidence for cross-talk between different classes of insulators, and for a broad role of the BEAF proteins in maintaining patterns of gene expression during eye development. Most identified genes encode other insulator binding proteins, transcription factors involved in head development, or general transcription factors. Because it is unlikely that insulator function is limited to eye development, the present results support the hypothesis that insulators play a widespread role in maintaining global transcription programs.
TLR4 stands at the forefront of innate immune responses, recognizing various pathogen- associated molecular patterns and endogenous ligands, thus serving as a pivotal mediator in the immune system's defense against infections and tissue damage. Beyond its canonical role in infection, emerging evidence highlights TLR4's involvement in numerous non-infectious human diseases, ranging from metabolic disorders to neurodegenerative conditions and cancer. Targeting TLR4 signaling pathways presents a promising therapeutic approach with broad applicability across these diverse pathological states.
E3 ubiquitin ligases have been linked to developmental diseases including autism, Angelman syndrome (UBE3A), and Johanson-Blizzard syndrome (JBS) (UBR1). Here, we report variants in the E3 ligase UBR5 in 29 individuals presenting with a neurodevelopmental syndrome that includes developmental delay, autism, intellectual disability, epilepsy, movement disorders, and/or genital anomalies. Their phenotype is distinct from JBS due to the absence of exocrine pancreatic insufficiency and the presence of autism, epilepsy, and, in some probands, a movement disorder.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address:
How specific enhancer-promoter pairing is established remains mostly unclear. Besides the CTCF/cohesin machinery, few nuclear factors have been studied for a direct role in physically connecting regulatory elements. Using a murine erythroid cell model, we show via acute degradation experiments that LDB1 directly and broadly promotes connectivity among regulatory elements.
Polymyxin B is one of the last lines of defense in infections caused by multidrug-resistant Gram-negative bacteria. Aeromonas hydrophila are important fish pathogens and the occurrence of polymyxin B-resistant A. hydrophila isolates is increasing.
Objectives: To determine ADHD research priorities from the perspective of ADHD professionals internationally.
Method: A two-stage modified Delphi design was used. In Stage 1 (qualitative), participants listed research questions relating to ADHD that they perceived to be most important ( = 132).
