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ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma
Babikir, H., Wang, L., Shamardani, K. et al.
Background
Recent single-cell transcriptomic studies report that IDH-mutant gliomas share a common hierarchy of cellular phenotypes, independent of genetic subtype. However, the genetic differences between IDH-mutant glioma subtypes are prognostic, predictive of response to chemotherapy, and correlate with distin... |
Genetic perturbation of PU.1 binding and chromatin looping at neutrophilenhancers associates with autoimmune disease.
Watt, Stephen et al.
Neutrophils play fundamental roles in innate immune response, shape adaptive immunity, and are a potentially causal cell type underpinning genetic associations with immune system traits and diseases. Here, we profile the binding of myeloid master regulator PU.1 in primary neutrophils across nearly a hundred voluntee... |
Fra-1 regulates its target genes via binding to remote enhancers withoutexerting major control on chromatin architecture in triple negative breastcancers.
Bejjani, Fabienne and Tolza, Claire and Boulanger, Mathias and Downes,Damien and Romero, Raphaël and Maqbool, Muhammad Ahmad and Zine ElAabidine, Amal and Andrau, Jean-Christophe and Lebre, Sophie and Brehelin,Laurent and Parrinello, Hughes and Rohmer,
The ubiquitous family of dimeric transcription factors AP-1 is made up of Fos and Jun family proteins. It has long been thought to operate principally at gene promoters and how it controls transcription is still ill-understood. The Fos family protein Fra-1 is overexpressed in triple negative breast cancers (TNBCs) w... |
Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.
Kern C. et al.
Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticate... |
STAG proteins promote cohesin ring loading at R-loops
Porter, H. et al.
Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not a mere passenger in this structure, but instead plays a key role in co... |
Environmental enrichment induces epigenomic and genome organization changesrelevant for cognitive function
Espeso-Gil, S. et al.
In early development, the environment triggers mnemonic epigenomic programs resulting in memory and learning experiences to confer cognitive phenotypes into adulthood. To uncover how environmental stimulation impacts the epigenome and genome organization, we used the paradigm of environmental enrichment (EE) in youn... |
Postoperative abdominal sepsis induces selective and persistent changes inCTCF binding within the MHC-II region of human monocytes.
Siegler B. et al.
BACKGROUND: Postoperative abdominal infections belong to the most common triggers of sepsis and septic shock in intensive care units worldwide. While monocytes play a central role in mediating the initial host response to infections, sepsis-induced immune dysregulation is characterized by a defective antigen present... |
Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.
Chen C. et al.
Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50\% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection... |
Integrative Omics Analyses Reveal Epigenetic Memory in Diabetic Renal CellsRegulating Genes Associated With Kidney Dysfunction.
Bansal, A and Balasubramanian, S and Dhawan, S and Leung, A and Chen, Z andNatarajan, R
Diabetic kidney disease (DKD) is a major complication of diabetes and the leading cause of end-stage renal failure. Epigenetics has been associated with metabolic memory, in which prior periods of hyperglycemia enhance the future risk of developing DKD despite subsequent glycemic control. To understand the mechanist... |
Preformed chromatin topology assists transcriptional robustness of during limb development.
Paliou C, Guckelberger P, Schöpflin R, Heinrich V, Esposito A, Chiariello AM, Bianco S, Annunziatella C, Helmuth J, Haas S, Jerković I, Brieske N, Wittler L, Timmermann B, Nicodemi M, Vingron M, Mundlos S, Andrey G
Long-range gene regulation involves physical proximity between enhancers and promoters to generate precise patterns of gene expression in space and time. However, in some cases, proximity coincides with gene activation, whereas, in others, preformed topologies already exist before activation. In this study, we inves... |
High-throughput ChIPmentation: freely scalable, single day ChIPseq data generation from very low cell-numbers.
Gustafsson C, De Paepe A, Schmidl C, Månsson R
BACKGROUND: Chromatin immunoprecipitation coupled to sequencing (ChIP-seq) is widely used to map histone modifications and transcription factor binding on a genome-wide level. RESULTS: We present high-throughput ChIPmentation (HT-ChIPmentation) that eliminates the need for DNA purification prior to library amplifica... |
DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes
Nothjunge S. et al.
Storage of chromatin in restricted nuclear space requires dense packing while ensuring DNA accessibility. Thus, different layers of chromatin organization and epigenetic control mechanisms exist. Genome-wide chromatin interaction maps revealed large interaction domains (TADs) and higher order A and B compartments, r... |
High Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure
Rosa-Garrido M. et al.
Background -Cardiovascular disease is associated with epigenomic changes in the heart, however the endogenous structure of cardiac myocyte chromatin has never been determined. Methods -To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequenc... |
Platelet function is modified by common sequence variation in megakaryocyte super enhancers
Petersen R. et al.
Linking non-coding genetic variants associated with the risk of diseases or disease-relevant traits to target genes is a crucial step to realize GWAS potential in the introduction of precision medicine. Here we set out to determine the mechanisms underpinning variant association with platelet quantitative traits usi... |
Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma
Shen CH et al.
The protein kinase B-Raf proto-oncogene, serine/threonine kinase (BRAF) is an oncogenic driver and therapeutic target in melanoma. Inhibitors of BRAF (BRAFi) have shown high response rates and extended survival in patients with melanoma who bear tumors that express mutations encoding BRAF proteins mutant at Val600, ... |
