Examining NF-κB genomic interactions by ChIP-seq and CUT&Tag.

An understanding of the mechanisms and logic by which transcription factors coordinate gene regulation requires delineation of their genomic interactions at a genome-wide scale. Chromatin immunoprecipitation-sequencing (ChIP-seq) and more recent techniques, including CUT&Tag, typically reveal thousands of genomic interactions by transcription factors, but without insight into their functional roles. Due to cost and time considerations, optimization of ChIP experimental conditions is typically carried out only with representative interaction sites rather than through genome-wide analyses.

Selective regulation of a defined subset of inflammatory and immunoregulatory genes by an NF-κB p50-IκBζ pathway.

The five NF-κB family members and three nuclear IκB proteins play important biological roles, but the mechanisms by which distinct members of these protein families contribute to selective gene transcription remain poorly understood, especially at a genome-wide scale. Using nascent transcript RNA-seq, we observed considerable overlap between p50-dependent and IκBζ-dependent genes in Toll-like receptor 4 (TLR4)-activated macrophages. Key immunoregulatory genes, including , , , and are among the p50-IκBζ-codependent genes.

Opposing tumor-cell-intrinsic and -extrinsic roles of the IRF1 transcription factor in antitumor immunity.

Type I interferon (IFN-I) and IFN-γ foster antitumor immunity by facilitating T cell responses. Paradoxically, IFNs may promote T cell exhaustion by activating immune checkpoints. The downstream regulators of these disparate responses are incompletely understood.

IL-10 constrains sphingolipid metabolism to limit inflammation.

Interleukin-10 (IL-10) is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types. Loss of IL-10 signalling results in life-threatening inflammatory bowel disease in humans and mice-however, the exact mechanism by which IL-10 signalling subdues inflammation remains unclear. Here we find that increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10 deficiency.

Multicentric Reticulohistiocytosis-A rare and disabling disease.

Multicentric reticulohistiocytosis is a rare multisystemic condition associated with papulonodular skin lesions, severe arthritis and malignancy. Histopathology shows histiocytes containing abundant eosinophilic ground glass cytoplasm and multinucleated giant cells. Early recognition, age-appropriate malignancy work-up and treatment is important to prevent impairment of daily life activity.

IL-10 constrains sphingolipid metabolism via fatty acid desaturation to limit inflammation.

Unchecked chronic inflammation is the underlying cause of many diseases, ranging from inflammatory bowel disease to obesity and neurodegeneration. Given the deleterious nature of unregulated inflammation, it is not surprising that cells have acquired a diverse arsenal of tactics to limit inflammation. IL-10 is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types; however, the exact mechanism by which IL-10 signaling subdues inflammation remains unclear.

Cold Spring Harbor Laboratory 2022: emerging insights and viewpoints in immunology.

Some of the current and former organizers of the Cold Spring Harbor Laboratory (CSHL) 'Gene Expression and Signaling in the Immune System' (GESIS) meeting offer opinions on emerging questions in immunology, discussing the strong value of this recurring scientific meeting in the field.

Hepatic GATA4 regulates cholesterol and triglyceride homeostasis in collaboration with LXRs.

GATA4 is a transcription factor known for its crucial role in the development of many tissues, including the liver; however, its role in adult liver metabolism is unknown. Here, using high-throughput sequencing technologies, we identified GATA4 as a transcriptional regulator of metabolism in the liver. GATA4 expression is elevated in response to refeeding, and its occupancy is increased at enhancers of genes linked to fatty acid and lipoprotein metabolism.

Oct4:Sox2 binding is essential for establishing but not maintaining active and silent states of dynamically regulated genes in pluripotent cells.

Much has been learned about the mechanisms of action of pluripotency factors Oct4 and Sox2. However, as with other regulators of cell identity, little is known about the impact of disrupting their binding motifs in a native environment or the characteristics of genes they regulate. By quantitatively examining dynamic ranges of gene expression instead of focusing on conventional measures of differential expression, we found that Oct4 and Sox2 enhancer binding is strongly enriched near genes subject to large dynamic ranges of expression among cell types, with binding sites near these genes usually within superenhancers.

Allogeneic hematopoietic stem cell transplantation: lessons learned by a molecular immunologist/transplant patient.

Much has been learned about the genes and pathways that contribute to a diverse array of hematopoietic malignancies and other hematopoietic diseases. However, for many of these diseases, an allogeneic hematopoietic stem cell (HSC) transplant remains the preferred treatment option. This opinion article provides the perspective of a molecular immunologist who became a transplant patient after many years studying basic mechanisms of blood cell development.

Suppressing fatty acid synthase by type I interferon and chemical inhibitors as a broad spectrum anti-viral strategy against SARS-CoV-2.

SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic. As part of the innate immune response to viral infection, type I interferons (IFN-I) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes (ISGs), that collectively foster an antiviral state. We report here the identification of a group of type I interferon suppressed genes, including fatty acid synthase (FASN), which are involved in lipid metabolism.

TPL-2 Inhibits IFN-β Expression via an ERK1/2-TCF-FOS Axis in TLR4-Stimulated Macrophages.

TPL-2 kinase plays an important role in innate immunity, activating ERK1/2 MAPKs in myeloid cells following TLR stimulation. We investigated how TPL-2 controls transcription in TLR4-stimulated mouse macrophages. TPL-2 activation of ERK1/2 regulated expression of genes encoding transcription factors, cytokines, chemokines, and signaling regulators.

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study.

Background: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut-brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut-brain axis.

Species-Specific Relationships between DNA and Chromatin Properties of CpG Islands in Embryonic Stem Cells and Differentiated Cells.

CpG islands often exhibit low DNA methylation, high histone H3 lysine 4 trimethylation, low nucleosome density, and high DNase I hypersensitivity, yet the rules by which CpG islands are sensed remain poorly understood. In this study, we first evaluated the relationships between the DNA and the chromatin properties of CpG islands in embryonic stem cells using modified bacterial artificial chromosomes. Then, using a bioinformatic approach, we identified strict CpG-island density and length thresholds in mouse embryonic stem and differentiated cells that consistently specify low DNA methylation levels.

Observation of a transition between dynamical phases in a quantum degenerate Fermi gas.

A proposed paradigm for out-of-equilibrium quantum systems is that an analog of quantum phase transitions exists between parameter regimes of qualitatively distinct time-dependent behavior. Here, we present evidence of such a transition between dynamical phases in a cold-atom quantum simulator of the collective Heisenberg model. Our simulator encodes spin in the hyperfine states of ultracold fermionic potassium.

Single cell analysis reveals immune cell-adipocyte crosstalk regulating the transcription of thermogenic adipocytes.

Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance.

Global research trends in microbiome-gut-brain axis during 2009-2018: a bibliometric and visualized study.

Background: The pathways and mechanism by which associations between the gut microbiome and the brain, termed the microbiome-gut-brain axis (MGBA), are manifest but remain to be fully elucidated. This study aims to use bibliometric analysis to estimate the global activity within this rapidly developing field and to identify particular areas of focus that are of current relevance to the MGBA during the last decade (2009-2018).

Methods: The current study uses the Scopus for data collection.

Dissection of acute stimulus-inducible nucleosome remodeling in mammalian cells.

Accessibility of the genomic regulatory information is largely controlled by the nucleosome-organizing activity of transcription factors (TFs). While stimulus-induced TFs bind to genomic regions that are maintained accessible by lineage-determining TFs, they also increase accessibility of thousands of -regulatory elements. Nucleosome remodeling events underlying such changes and their interplay with basal positioning are unknown.

Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming.

Background: Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse.

Results: To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems.