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Articles by Epigenetics Programme
Epigenetic priming of mammalian embryonic enhancer elements coordinates developmental gene networks - Genome Biology
Human-induced pluripotent stem cell (hiPSC) lines (HPSI1113i-bima_1, HPSI0114i-kolf_2, HPSI0114i-kolf_3, HPSI0214i-kucg_2, HPSI0514i-letw_5, HPSI1113i-podx_1, HPSI1113i-qolg_1, HPSI0314i-sojd_3, HPSI0214i-wibj_2, and HPSI0215i-yoch_6) were purchased from the Human Induced Pluripotent Stem Cells Initiative (HipSci; https://www.hipsci.org/), deposited by the Wellcome Trust Sanger Institute (https://www.sanger.ac.uk/), and banked at European Collection of Authenticated Cell Cultures (ECACC).
DNA G-quadruplex structures act as functional elements in α- and β-globin enhancers - Genome Biology
K562 cells (ATCC) were cultured in RPMI1640 (Glutamine plus, Life Technologies) with 10% of fetal bovine serum (Life Technologies) at 37 °C with 5% CO2. Cell cultures were routinely checked for mycoplasma infection. Cells were not further authenticated. Bulk CUT&Tag was conducted as previously described [10, 38].
Pro-cumulin addition in a biphasic in vitro oocyte maturation system modulates human oocyte and cumulus cell transcriptomes
Biphasic in vitro oocyte maturation (IVM) can be offered as a patient-friendly alternative to conventional ovarian stimulation in in vitro fertilization (IVF) patients predicted to be hyper-responsive to ovarian stimulation. However, cumulative live birth rates after IVM per cycle are lower than after conventional ovarian stimulation for IVF.
Improved simultaneous mapping of epigenetic features and 3D chromatin structure via ViCAR - Genome Biology
References Lieberman-Aiden E, Van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 1979;2009(326):289–93. Google Scholar Tolhuis B, Palstra R-J, Splinter E, Grosveld F, De Laat W. Looping and interaction between hypersensitive sites in the active beta-globin locus. Mol Cell. 2002;10:1453–65.
Dietary change without caloric restriction maintains a youthful profile in ageing yeast
Loading metrics Open Access Peer-reviewed Research Article Citation: Horkai D, Hadj-Moussa H, Whale AJ, Houseley J (2023) Dietary change without caloric restriction maintains a youthful profile in ageing yeast. PLoS Biol 21(8): e3002245. https://doi.org/10.1371/journal.pbio.3002245 Academic Editor: Sarah E. Zanders, Stowers Institute for Medical Research, UNITED STATES Received: August 15, 2022; Accepted: July 12, 2023; Published: August 29, 2023 Copyright: © 2023 Horkai et al.
Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation
Loading metrics Open Access Peer-reviewed Research Article Citation: Zylstra A, Hadj-Moussa H, Horkai D, Whale AJ, Piguet B, Houseley J (2023) Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation. PLoS Biol 21(8): e3002250. https://doi.org/10.1371/journal.pbio.3002250 Academic Editor: Sarah E.
Single-cell multi-omics profiling links dynamic DNA methylation to cell fate decisions during mouse early organogenesis - Genome Biology
Code to reproduce the results in this manuscript is available via GitHub repositories for each of the three sets of analysis: DNMT scRNA-seq [61], Tet-TKO scRNA-seq [62] and -TKO scNMT-seq [63]. Stable versions of all three repositories have been archived on Zenodo under a MIT Licence [64]. Raw sequencing data together with processed files are available in the Gene Expression Omnibus under accession GSE204908 [65].
Amniogenesis occurs in two independent waves in primates
Highlights • The amnion develops in two distinct waves of epiblast differentiation in primates • The amniotic cavity is formed during the early wave via a trophectoderm-like route • Late amniogenesis follows a nonneural ectoderm-like transcriptional program • Differentiation of hPSC from different states models the two waves of amniogenesis Summary In primates, the amnion emerges through cavitation of the epiblast during implantation, whereas in other species it does so later at gastrulation...
8C-like cells capture the human zygotic genome activation program in vitro
Highlights • ZGA genes and transposable elements are expressed in 8CLCs but not in naive stem cells • DUX4 overexpression and spliceosome inhibition induce ZGA-like transcription • 8CLC marker proteins TPRX1 and H3.Y are expressed in 8-cell human embryos • 8CLCs can be used to study human ZGA-like programs in vitro Summary The activation of the embryonic genome marks the first major wave of transcription in the developing organism.
Identifying temporal and spatial patterns of variation from multimodal data using MEFISTO - Nature Methods
Abstract Factor analysis is a widely used method for dimensionality reduction in genome biology, with applications from personalized health to single-cell biology. Existing factor analysis models assume independence of the observed samples, an assumption that fails in spatio-temporal profiling studies. Here we present MEFISTO, a flexible and versatile toolbox for modeling high-dimensional data when spatial or temporal dependencies between the samples are known.
The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth
Highlights • Fetus-derived IGF2 controls placental microvasculature expansion in late gestation • The angiocrine effects of IGF2 are mediated via angiopoietins/Tek and IGF2R-ERK1/2 • Fetus-derived IGF2 also regulates trophoblast morphogenesis via Gcm1 and Synb • The imprinted Igf2-Igf2r axis matches placental development to fetal demand Summary In all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how the latter adapts to putative fetal signals...
Sex-specific chromatin remodelling safeguards transcription in germ cells - Nature
Abstract Stability of the epigenetic landscape underpins maintenance of the cell-type-specific transcriptional profile. As one of the main repressive epigenetic systems, DNA methylation has been shown to be important for long-term gene silencing; its loss leads to ectopic and aberrant transcription in differentiated cells and cancer1. The developing mouse germ line endures global changes in DNA methylation in the absence of widespread transcriptional activation.
Mutational synergy during leukemia induction remodels chromatin accessibility, histone modifications and three-dimensional DNA topology to alter gene expression | Nature Genetics
Abstract Altered transcription is a cardinal feature of acute myeloid leukemia (AML); however, exactly how mutations synergize to remodel the epigenetic landscape and rewire three-dimensional DNA topology is unknown. Here, we apply an integrated genomic approach to a murine allelic series that models the two most common mutations in AML: Flt3-ITD and Npm1c.
Integration of spatial and single-cell transcriptomic data elucidates mouse organogenesis - Nature Biotechnology
Abstract Molecular profiling of single cells has advanced our knowledge of the molecular basis of development. However, current approaches mostly rely on dissociating cells from tissues, thereby losing the crucial spatial context of regulatory processes. Here, we apply an image-based single-cell transcriptomics method, sequential fluorescence in situ hybridization (seqFISH), to detect mRNAs for 387 target genes in tissue sections of mouse embryos at the 8–12 somite stage.
Author Correction: Community-wide hackathons to identify central themes in single-cell multi-omics - Genome Biology
Author Correction Open Access Published: 25 August 2021 Kim-Anh Lê Cao1, Al J. Abadi1, 2, Lauren Hsu3,4, Arshi Arora5, Alexis Coullomb6, Atul Deshpande7, Yuzhou Feng1, Pratheepa Jeganathan8, Melanie Loth7, Chen Meng9, Wancen Mu10, Vera Pancaldi6,11, Kris Sankaran12, Dario Righelli13, Amrit Singh14,15, Joshua S. Sodicoff16,17, 2,7,18,19, 20, Joshua D. Welch16,21, Yue You22,23, Ricard Argelaguet24, Vincent J. Carey25, Ruben Dries26,27,28, Casey S. Greene29, Susan Holmes30, Michael I.
Community-wide hackathons to identify central themes in single-cell multi-omics - Genome Biology
Kim-Anh Lê Cao1, Al J. Abadi1, 2, Lauren Hsu3,28, Arshi Arora4, Alexis Coullomb5, Atul Deshpande6, Yuzhou Feng1, Pratheepa Jeganathan25, Melanie Loth6, Chen Meng26, Wancen Mu7, Vera Pancaldi5,8, Kris Sankaran9, Amrit Singh10,29, Joshua S. Sodicoff11,12, 2,6,13,30, 14, Joshua D. Welch11,15, Yue You16,31, Ricard Argelaguet17, Vincent J. Carey18, Ruben Dries19,32,33, Casey S. Greene20, Susan Holmes21, Michael I. Love7,27, Matthew E. Ritchie16,22,31, Guo-Cheng Yuan23, Aedin C.
Computational principles and challenges in single-cell data integration
1. Navin, N. E. The first five years of single-cell cancer genomics and beyond. Genome Res. 25, 1499–1507 (2015). CAS PubMed PubMed Central Article Google Scholar 2. Peng, G., Cui, G., Ke, J. & Jing, N. Using single-cell and spatial transcriptomes to understand stem cell lineage specification during early embryo development. Annu. Rev. Genomics Hum. Genet. 21, 163–181 (2020). CAS PubMed Article PubMed Central Google Scholar 3. Clark, S. J. et al.
Genome-wide analysis of DNA replication and DNA double-strand breaks using TrAEL-seq
Loading metrics Neesha Kara, Felix Krueger, Peter Rugg-Gunn, Jonathan Houseley Neesha Kara, Felix Krueger, Peter Rugg-Gunn, Jonathan Houseley Published: March 24, 2021 https://doi.org/10.1371/journal.pbio.3000886 ? This is an uncorrected proof. Figures Abstract Faithful replication of the entire genome requires replication forks to copy large contiguous tracts of DNA, and sites of persistent replication fork stalling present a major threat to genome stability.
Active turnover of DNA methylation during cell fate decisions
Abstract DNA methylation is a key layer of epigenetic regulation. The deposition of methylation marks relies on the catalytic activity of DNA methyltransferases (DNMTs), and their active removal relies on the activity of ten–eleven translocation (TET) enzymes. Paradoxically, in important biological contexts these antagonistic factors are co-expressed and target overlapping genomic regions.
TET1 and 5-Hydroxymethylation Preserve the Stem Cell State of Mouse Trophoblast
Highlights • 5hmC to 5mC ratios correlate with gene activity in TS cells • TS cell differentiation-associated loss of 5hmC is slowed down in hypoxia • TET1 binding in TS cells forms long-range interactions with key trophoblast genes • Intergenic TET1 binding sites in TS cells demarcate putative trophoblast enhancers Summary The ten-eleven translocation factor TET1 and its conferred epigenetic modification 5-hydroxymethylcytosine (5hmC) have important roles in maintaining the pluripotent state...
Cell-Surface Proteomics Identifies Differences in Signaling and Adhesion Protein Expression between Naive and Primed Human Pluripotent Stem Cells
Highlights • Direct measurement of plasma membrane proteins in two human pluripotent states • Proteomic resource contains quantitative analysis of signaling and adhesion proteins • Multiple cytokine receptors upstream of JAK-STAT pathway identified in naive cells • Functional experiments reveal FOLR1 and SUSD2 are not required for naive pluripotency Summary Naive and primed human pluripotent stem cells (hPSC) provide valuable models to study cellular and molecular developmental processes.
Network analysis of promoter interactions reveals the hierarchical differences in genome organisation between human pluripotent states
SUMMARY A complex and poorly understood interplay between 3D genome organisation, transcription factors and chromatin state underpins cell identity. To gain a systems-level understanding of this interplay, we generated a high-resolution atlas of annotated chromatin interactions in naïve and primed human pluripotent stem cells and developed a network-graph approach to examine the atlas at multiple spatial scales.
Transcription-induced formation of extrachromosomal DNA during yeast ageing
Loading metrics Open Access Peer-reviewed Research Article Ryan M. Hull, Michelle King, Grazia Pizza, Felix Krueger, Xabier Vergara, Jonathan Houseley Ryan M.
Transcription factors make the right contacts
Cell identity is shaped by a complex interplay between transcription factors, enhancers and genome organisation. A study now reveals a dynamic role for the transcription factor KLF4 in directing gene regulatory interactions during pluripotent cell reprogramming, demonstrating that transcription factors can function as chromatin organisers. Fig. 1: The transcription factor KLF4 directs enhancer–promoter interactions in mouse pluripotent stem cells. References 1. Takahashi, K. & Yamanaka, S.
Genomic Imprinting and Physiological Processes in Mammals
Complex multicellular organisms, such as mammals, express two complete sets of chromosomes per nucleus, combining the genetic material of both parents. However, epigenetic studies have demonstrated violations to this rule that are necessary for mammalian physiology; the most notable parental allele expression phenomenon is genomic imprinting.
Long-Range Enhancer Interactions Are Prevalent in Mouse Embryonic Stem Cells and Are Reorganized upon Pluripotent State Transition
Rewiring of the SE Interactome upon Pluripotent State Transition Long-Range SE Interactions Are Detected in ESCs, but Not in EpiSCs Long-Range Regulatory Contacts in ESCs Are Enriched for NANOG Occupancy In recent years, a subset of regulatory elements termed SEs have gained attention across a wide range of research fields (Hnisz et al., 2013xSuper-enhancers in the control of cell identity and disease.
Single-cell epigenomics: Recording the past and predicting the future
Single-cell multi-omics has recently emerged as a powerful technology by which different layers of genomic output—and hence cell identity and function—can be recorded simultaneously. Integrating various components of the epigenome into multi-omics measurements allows for studying cellular heterogeneity at different time scales and for discovering new layers of molecular connectivity between the genome and its functional output.
Genomic imprinting beyond DNA methylation: a role for maternal histones
To understand the additional components contributing to intergenerational epigenetic regulation, Inoue et al. [1] undertook a genome-wide characterisation of allelic gene expression and chromatin accessibility in early mouse development, focusing on the one-cell zygote, two-cell embryo and morula-stage embryo.
Single-Cell Landscape of Transcriptional Heterogeneity and Cell Fate Decisions during Mouse Early Gastrulation
Single-Cell Transcriptomics and Lineage Identification in E3.5, E4.5, E5.5, and E6.5 Embryos Reactivation and Subsequent Inactivation of the X Chromosome Symmetry Breaking in the Epiblast and PrE Transition In this study, we applied single-cell RNA-seq at a detailed level of resolution to explore early mouse development from pre-implantation to early gastrulation. Besides this valuable resource for the community, our study makes a number of important observations.
Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells
Global Demethylation Kinetics in Mutants of the DNA Methylation Machinery UHRF1 Is Downregulated at the Protein Level during the Serum-to-2i Transition UHRF1 Recruitment to Replication Foci Is Impaired in 2i ESCs The increased levels of 5hmC during the serum-to-2i conversion as well as publications showing further TET-dependent hypomethylation in vitamin C (vitC)-treated 2i ESCs (Blaschke et al., 2013xVitamin C induces Tet-dependent DNA demethylation and a blastocyst-like state in ES cells.
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