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2 months ago | 
nature.com | Michael Snyder |Hayan Lee |Annika K Weimer |Aaron M Horning |Edward D. Esplin |Kristina Ayers Paul | +4 more
Correction to: Nature Cancer https://doi.org/10.1038/s43018-024-00823-z, published online 30 October 2024. In the version of the article initially published, a technique described as “intact Micro-C” should have been called “MNase-digested Intact Hi-C” and has now been corrected throughout the article.
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Nov 21, 2024 | 
genome.cshlp.org | Samuel Kim |Georgi K. Marinov |William J. Greenleaf |Chan Zuckerberg Biohub
2 1 Stanford University; 2 Stanford University, Chan Zuckerberg Biohub ↵* Corresponding author; email: marinovg{at}stanford.edu Received May 24, 2024. Accepted November 19, 2024. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see https://genome.cshlp.org/site/misc/terms.xhtml).
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Oct 30, 2024 | 
nature.com | Hayan Lee |Annika K Weimer |Aaron M Horning |Edward D. Esplin |Kristina Ayers Paul |Thomas V. Karathanos | +3 more
AbstractAlthough three-dimensional (3D) genome architecture is crucial for gene regulation, its role in disease remains elusive. We traced the evolution and malignant transformation of colorectal cancer (CRC) by generating high-resolution chromatin conformation maps of 33 colon samples spanning different stages of early neoplastic growth in persons with familial adenomatous polyposis (FAP).
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Oct 30, 2024 | 
nature.com | Edward D. Esplin |Casey Hanson |Aaron M Horning |Hayan Lee |Aziz K. Khan |Annika K Weimer | +5 more
AbstractFamilial adenomatous polyposis (FAP) is a genetic disease causing hundreds of premalignant polyps in affected persons and is an ideal model to study transitions of early precancer states to colorectal cancer (CRC). We performed deep multiomic profiling of 93 samples, including normal mucosa, benign polyps and dysplastic polyps, from six persons with FAP.
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Jun 6, 2024 | 
biorxiv.org | Georgi K. Marinov |Vivekanandan Ramalingam |William J. Greenleaf |Anshul Kundaje
AbstractIn most eukaryotes, mitochondrial organelles contain their own genome, usually circular, which is the remnant of the genome of the ancestral bacterial endosymbiont that gave rise to modern mitochondria. Mitochondrial genomes are dramatically reduced in their gene content due to the process of endosymbiotic gene transfer to the nucleus; as a result most mitochondrial proteins are encoded in the nucleus and imported into mitochondria.
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May 15, 2024 | 
nature.com | Xue Sun |Atif Ahmed Siddiqui |Georgi K. Marinov |Sagiv Shifman |David Zucker |Adi Oron-Gottesman | +7 more
Classical evolutionary theories propose tradeoffs among reproduction, damage repair and lifespan. However, the specific role of the germline in shaping vertebrate aging remains largely unknown. In this study, we used the turquoise killifish (Nothobranchius furzeri) to genetically arrest germline development at discrete stages and examine how different modes of infertility impact life history. We first constructed a comprehensive single-cell gonadal atlas, providing cell-type-specific markers for downstream phenotypic analysis. We show here that germline depletion—but not arresting germline differentiation—enhances damage repair in female killifish. Conversely, germline-depleted males instead showed an extension in lifespan and rejuvenated metabolic functions. Through further transcriptomic analysis, we highlight enrichment of pro-longevity pathways and genes in germline-depleted male killifish and demonstrate functional conservation of how these factors may regulate longevity in germline-depleted Caenorhabditis elegans. Our results, therefore, demonstrate that different germline manipulation paradigms can yield pronounced sexually dimorphic phenotypes, implying alternative responses to classical evolutionary tradeoffs. Moses, Atlan et al. profile the killifish (Nothobranchius furzeri) gonad using single-cell sequencing and reveal that genetic germline depletion induces sexually dimorphic phenotypes, enhancing lifespan in male fish and somatic repair in females.
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May 7, 2024 | 
biorxiv.org | Samuel Kim |Georgi K. Marinov |William J. Greenleaf
AbstractGene regulation in most eukaryotes involves two fundamental physical processes -- alterations in the packaging of the genome by nucleosomes, with active cis-regulatory elements (CREs) generally characterized by an open-chromatin configuration, and the activation of transcription.
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Mar 19, 2024 | 
nature.com | David Yao |Josh Tycko |Lexi R. Bounds |Benjamin Doughty |Alexander White |Xingjie Ren | +16 more
AbstractThe ENCODE Consortium’s efforts to annotate noncoding cis-regulatory elements (CREs) have advanced our understanding of gene regulatory landscapes. Pooled, noncoding CRISPR screens offer a systematic approach to investigate cis-regulatory mechanisms. The ENCODE4 Functional Characterization Centers conducted 108 screens in human cell lines, comprising >540,000 perturbations across 24.85 megabases of the genome.
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Nov 2, 2023 | 
biorxiv.org | Georgi K. Marinov |Benjamin Doughty |Anshul Kundaje |William J. Greenleaf
AbstractHistone proteins have traditionally been thought to be restricted to eukaryotes and most archaea, with eukaryotic nucleosomal histones deriving from their archaeal ancestors. In contrast, bacteria lack histones as a rule. However, histone proteins have recently been identified in a few bacterial clades, most notably the phylum Bdellovibrionota, and these histones have been proposed to exhibit a range of divergent features compared to histones in archaea and eukaryotes.
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Sep 28, 2023 | 
nature.com | Owen Smith |William J. Greenleaf
AbstractNon-coding RNAs (ncRNAs) are transcribed throughout the genome and provide regulatory inputs to gene expression through their interaction with chromatin. Yet, the genomic targets and functions of most ncRNAs are unknown. Here we use chromatin-associated RNA sequencing (ChAR-seq) to map the global network of ncRNA interactions with chromatin in human embryonic stem cells and the dynamic changes in interactions during differentiation into definitive endoderm.
