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Recurrent patterns of widespread neuronal genomic damage shared by major neurodegenerative disorders Zinan Zhou et al. Amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD) are common neurodegenerative disorders for which the mechanisms driving neuronal death remain unclear. Single-cell whole-genome sequencing of 429 neurons from three C9ORF72 ALS, six C9ORF72 FTD, seven AD, and twenty-thre... |
Diverse somatic genomic alterations in single neurons in chronic traumatic encephalopathy Guanlan Dong et al. Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is linked to exposure to repetitive head impacts (RHI), yet little is known about its pathogenesis. Applying two single-cell whole-genome sequencing methods to hundreds of neurons from prefrontal cortex of 15 individuals with CTE, and 4 with ... |
Combinatorial mapping of E3 ubiquitin ligases to their target substrates Chase C. Suiter et al.
Highlights
Developed a combinatorial assay to test E3-substrate interactions at scale
Identified known and unknown E3-substrate relationships across three screens
Assessment of in silico models points to scalable computational substrate discovery
Computed models of E3-... |
Minimization of gene editing off-target effects by tissue restriction of expression Nam-Gyun Kim et al. Therapeutic in vivo gene editing with highly specific nucleases has the potential to revolutionize treatment for a wide range of human diseases, including genetic disorders and latent viral infections like herpes simplex virus (HSV). However, challenges regarding specificity, efficiency, delivery, and safe... |
HIRA protects telomeres against R-loop-induced instability in ALT cancer cells Michelle Lee Lynskey et al.
Highlights
HIRA establishes greater telomeric chromatin accessibility after ATRX-DAXX loss
Deposition of new H3.3 by HIRA-UBN restricts telomeric ssDNA and TERRA R-loops
Unresolved TERRA R-loops block new H3.3 deposition by HIRA-UBN
CHK1 phosphorylation of H3.3 is critical to pr... |
Enhancing single-cell ATAC sequencing with formaldehyde fixation, cryopreservation, and multiplexing for flexible analysis Tobias Hohl et al. The assay for transposase-accessible chromatin using sequencing (ATAC-seq) revolutionized the field of epigenetics since its emergence by providing a means to uncover chromatin dynamics and other factors affecting gene expression. The development of single-cell (sc) applications in recent years led to an even deeper... |
On the identification of differentially-active transcription factors from ATAC-seq data Felix Ezequiel Gerbaldo et al. ATAC-seq has emerged as a rich epigenome profiling technique, and is commonly used to identify Transcription Factors (TFs) underlying given phenomena. A number of methods can be used to identify differentially-active TFs through the accessibility of their DNA-binding motif, however little is known on the best approa... |
HNF1β bookmarking involves Topoisomerase 1 activation and DNA topology relaxation in mitotic chromatin Alessia Bagattin et al.
Highlights
HNF1β mitotic site binding is preserved with a specific methanol/formaldehyde ChIP
BTBD2, an HNF1β partner, mediates mitosis-specific interaction with TOP1
HNF1β recruits TOP1 and induces DNA relaxation around bookmarked HNF1β sites
An HNF1β m... |
Rhabdomyosarcoma fusion oncoprotein initially pioneers a neural signature in vivo Jack Kucinski et al. Fusion-positive rhabdomyosarcoma is an aggressive pediatric cancer molecularly characterized by arrested myogenesis. The defining genetic driver, PAX3::FOXO1, functions as a chimeric gain-of-function transcription factor. An incomplete understanding of PAX3::FOXO1’s in vivo epigenetic mechanisms has hindered t... |
CRISPR screen decodes SWI/SNF chromatin remodeling complex assembly Hanna Schwaemmle et al. The SWI/SNF (or BAF) complex is an essential chromatin remodeler that regulates DNA accessibility at developmental genes and enhancers. SWI/SNF subunits are among the most frequently mutated genes in cancer and neurodevelopmental disorders. These mutations are often heterozygous loss-of-function alleles, indicating ... |
Clock-dependent chromatin accessibility rhythms regulate circadian transcription Ye Yuan et al. Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made in understanding the regulatory role of clock proteins in circadian rhythms, how chromatin organization affects circadian rhythms remains poorly ... |
PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites Andrew Dimond et al. PBK/TOPK is a mitotic kinase implicated in haematological and non-haematological cancers. Here we show that the key haemopoietic regulators Ikaros and Aiolos require PBK-mediated phosphorylation to dissociate from chromosomes in mitosis. Eviction of Ikaros is rapidly reversed by addition of the PBK-inhibitor OTS514,... |
Widespread impact of nucleosome remodelers on transcription at cis-regulatory elements Benjamin J. Patty et al. Nucleosome remodeling complexes and other regulatory factors work in concert to build a chromatin environment that directs the expression of a distinct set of genes in each cell using cis-regulatory elements (CREs), such as promoters and enhancers, that drive transcription of both mRNAs and CRE-associated non-coding... |
High-throughput sequencing of insect specimens with sub-optimal DNA preservation using a practical, plate-based Illumina-compatible Tn5 transposase library preparation method Cobb L. et all. Entomological sampling and storage conditions often prioritise efficiency, practicality and conservation of morphological characteristics, and may therefore be suboptimal for DNA preservation. This practice can impact downstream molecular applications, such as the generation of high-throughput genomic libraries, whi... |
On the identification of differentially-active transcription factors from ATAC-seq data Gerbaldo F. et al. ATAC-seq has emerged as a rich epigenome profiling technique, and is commonly used to identify Transcription Factors (TFs) underlying given phenomena. A number of methods can be used to identify differentially-active TFs through the accessibility of their DNA-binding motif, however little is known on the best approa... |
Improved metagenome assemblies through selective enrichment of bacterial genomic DNA from eukaryotic host genomic DNA using ATAC-seq Lindsey J Cantin et al. Genomics can be used to study the complex relationships between hosts and their microbiota. Many bacteria cannot be cultured in the laboratory, making it difficult to obtain adequate amounts of bacterial DNA and to limit host DNA contamination for the construction of metagenome-assembled genomes (MAGs). For example,... |
A fast and inexpensive plate-based NGS library preparation method for insect genomics Lauren Cobb et al. Entomological sampling and storage conditions often prioritise efficiency, practicality and conservation of morphological characteristics, and may therefore be suboptimal for DNA preservation. This practice can impact downstream molecular applications, such as the generation of high-throughput genomic libraries, whi... |
Therapeutic targeting of EP300/CBP by bromodomain inhibition in hematologic malignancies Luciano Nicosia et al. CCS1477 (inobrodib) is a potent, selective EP300/CBP bromodomain inhibitor which induces cell-cycle arrest and differentiation in hematologic malignancy model systems. In myeloid leukemia cells, it promotes rapid eviction of EP300/CBP from an enhancer subset marked by strong MYB occupancy and high H3K27 acetylation,... |
ARID1A governs the silencing of sex-linked transcription during male meiosis in the mouse Menon D.U. et al. We present evidence implicating the BAF (BRG1/BRM Associated Factor) chromatin remodeler in meiotic sex chromosome inactivation (MSCI). By immunofluorescence (IF), the putative BAF DNA binding subunit, ARID1A (AT-rich Interaction Domain 1a), appeared enriched on the male sex chromosomes during diplonema of meiosis I... |
CXCR4 signaling strength regulates hematopoietic multipotent progenitor fate through extrinsic and intrinsic mechanisms Vincent Rondeau et al. How cell-extrinsic niche-related and cell-intrinsic cues drive lineage specification of hematopoietic multipotent progenitors (MPPs) in the bone marrow (BM) is partly understood. We show that CXCR4 signaling strength regulates localization and fate of MPPs. In mice phenocopying the BM myeloid skewing of patients wit... |
YAP/BRD4-controlled ROR1 promotes tumor-initiating cells andhyperproliferation in pancreatic cancer. Yamazaki M. et al. Tumor-initiating cells are major drivers of chemoresistance and attractive targets for cancer therapy, however, their identity in human pancreatic ductal adenocarcinoma (PDAC) and the key molecules underlying their traits remain poorly understood. Here, we show that a cellular subpopulation with partial epithelial-m... |
A neurodevelopmental epigenetic programme mediated bySMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastomametastasis. Zou Han et al. How abnormal neurodevelopment relates to the tumour aggressiveness of medulloblastoma (MB), the most common type of embryonal tumour, remains elusive. Here we uncover a neurodevelopmental epigenomic programme that is hijacked to induce MB metastatic dissemination. Unsupervised analyses of integrated publicly availab... |
EBF1 is continuously required for stabilizing local chromatinaccessibility in pro-B cells. Zolotarev Nikolay et al. The establishment of de novo chromatin accessibility in lymphoid progenitors requires the "pioneering" function of transcription factor (TF) early B cell factor 1 (EBF1), which binds to naïve chromatin and induces accessibility by recruiting the BRG1 chromatin remodeler subunit. However, it remains unclear whet... |