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| Open AccessSynthetic reversed sequences reveal default genomic states
Introduction of a long synthetic DNA into yeast genomic loci results in high default transcriptional activity in yeast but low activity in mouse, suggesting distinct default levels of genomic activity in these organisms.
- Brendan R. Camellato
- , Ran Brosh
- & Jef D. Boeke
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Parental histone transfer caught at the replication fork
Structures of the yeast replisome associated with the FACT complex and an evicted histone hexamer offer insights into the mechanism of replication-coupled histone recycling for maintaining epigenetic inheritance.
- Ningning Li
- , Yuan Gao
- & Yuanliang Zhai
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Article
| Open AccessWNT signalling control by KDM5C during development affects cognition
The demethylase KDM5C, mutations in which often lead to intellectual disability, is identified as a crucial player in regulating the precise timing of neurodevelopment together with the WNT signalling pathway.
- Violetta Karwacki-Neisius
- , Ahram Jang
- & Yang Shi
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Coordination of cohesin and DNA replication observed with purified proteins
We study the interplay between cohesin and replication by reconstituting a functional replisome using purified proteins, showing how cohesin initially responds to replication and providing a molecular model for the establishment of sister chromatid cohesion.
- Yasuto Murayama
- , Shizuko Endo
- & Hiroyuki Araki
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| Open AccessSingle-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain
Methylome-based clustering and cross-modality integration with companion datasets from the BRAIN Initiative Cell Census Network enabled the construction of a 3D multi-omic genome atlas of the adult mouse brain featuring thousands of cell-type-specific profiles.
- Hanqing Liu
- , Qiurui Zeng
- & Joseph R. Ecker
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Asymmetric distribution of parental H3K9me3 in S phase silences L1 elements
The epigenetic modification H3K9me3 is asymmetrically partitioned at long interspersed nuclear element retrotransposons for their silencing in S phase, a newly discovered mechanism that is mediated by the HUSH complex and the DNA polymerase Pol ε.
- Zhiming Li
- , Shoufu Duan
- & Zhiguo Zhang
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TNRC18 engages H3K9me3 to mediate silencing of endogenous retrotransposons
Trinucleotide-repeat-containing 18 (TNRC18), which has poorly understood functions, is now identified as an H3K9me3-specific reader that silences endogenous retroviruses.
- Shuai Zhao
- , Jiuwei Lu
- & Gang Greg Wang
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Article
| Open AccessInhibition of fatty acid oxidation enables heart regeneration in adult mice
Inhibition of the fatty acid oxidation metabolic pathway through inactivation of Cpt1b enhances cardiomyocyte survival and proliferation and allows heart regeneration in adult mice.
- Xiang Li
- , Fan Wu
- & Thomas Braun
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Acetyl-methyllysine marks chromatin at active transcription start sites
Cellular lysine residues can be both methylated and acetylated on the same sidechain to form Nε-acetyl-Nε-methyllysine (Kacme), which is found on histone H4 across a range of species and across mammalian tissues and is associated with active chromatin.
- William J. Lu-Culligan
- , Leah J. Connor
- & Matthew D. Simon
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| Open AccessR-loop-dependent promoter-proximal termination ensures genome stability
SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability.
- Congling Xu
- , Chengyu Li
- & Fei Xavier Chen
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Article
| Open AccessCooperation between bHLH transcription factors and histones for DNA access
Cryo-EM structures and analysis provide insight into the mechanisms by which basic helix–loop–helix transcription factors access E-box DNA sequences that are embedded within nucleosomes, and cooperate with other transcription factors.
- Alicia K. Michael
- , Lisa Stoos
- & Nicolas H. Thomä
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| Open AccessEpigenetic dysregulation from chromosomal transit in micronuclei
Missegregated chromosomes that are sequestrated in micronuclei are subject to changes in histone modifications leading to abnormalities in chromatin accessibility that remain long after the chromosomes have been reincorporated into the primary nucleus.
- Albert S. Agustinus
- , Duaa Al-Rawi
- & Samuel F. Bakhoum
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| Open AccessHistone modifications regulate pioneer transcription factor cooperativity
Binding of the human pioneer transcription factor OCT4 to nucleosomes containing endogenous DNA sequences causes changes to the nucleosome structure and facilitates the cooperative assembly of multiple pioneer transcription factors, a property that can be affected by histone modifications.
- Kalyan K. Sinha
- , Silvija Bilokapic
- & Mario Halic
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Mitotic bookmarking by SWI/SNF subunits
Subunits of SWI/SNF act as mitotic bookmarks to safeguard cell identity during cell division.
- Zhexin Zhu
- , Xiaolong Chen
- & Charles W. M. Roberts
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Establishment and function of chromatin organization at replication origins
Genome-scale in vitro reconstitution of DNA replication through chromatin establishes a crucial role for the origin recognition complex in organizing nucleosome arrays that are crucial for the initiation of replication.
- Erika Chacin
- , Karl-Uwe Reusswig
- & Christoph F. Kurat
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| Open AccessWhole-genome doubling drives oncogenic loss of chromatin segregation
Whole-genome doubling induces the loss of segregation of chromatin compartments, and can lead to tumour-promoting epigenetic and transcriptional modifications.
- Ruxandra A. Lambuta
- , Luca Nanni
- & Elisa Oricchio
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BRD8 maintains glioblastoma by epigenetic reprogramming of the p53 network
BRD8 is identified as a specific epigenetic vulnerability for glioblastomas that harbour wild-type p53.
- Xueqin Sun
- , Olaf Klingbeil
- & Alea A. Mills
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Structural variants drive context-dependent oncogene activation in cancer
Results are presented that indicate that alterations to gene regulatory three-dimensional architecture are a critical mechanism that enables structural variant-based oncogene activation in cancer genomes and sheds light on the essential elements for such gene activation events.
- Zhichao Xu
- , Dong-Sung Lee
- & Jesse R. Dixon
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| Open AccessHistone H2B.8 compacts flowering plant sperm through chromatin phase separation
H2B.8 is identified as a histone variant that mediates a newly described mechanism of transcription-compatible chromatin condensation in flowering plant sperm cells.
- Toby Buttress
- , Shengbo He
- & Xiaoqi Feng
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Structure of the NuA4 acetyltransferase complex bound to the nucleosome
The cryo-electron microscopy structure of NuA4 from Saccharomyces cerevisiae bound to the nucleosome illustrates how NuA4 is assembled and provides mechanistic insights into nucleosome recognition and transcription co-activation by a histone acetyltransferase.
- Keke Qu
- , Kangjing Chen
- & Zhucheng Chen
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cBAF complex components and MYC cooperate early in CD8+ T cell fate
cBAF is a negative determinant of memory T cell fate and the manipulation of cBAF early in T cell differentiation can improve cancer immunotherapy.
- Ao Guo
- , Hongling Huang
- & Douglas R. Green
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| Open AccessCohesin-mediated loop anchors confine the locations of human replication origins
A study shows that the three-dimensional conformation of the human genome influences the positioning of DNA replication initiation zones, highlighting cohesin-mediated loop anchors as essential determinants of their precise location.
- Daniel J. Emerson
- , Peiyao A. Zhao
- & Jennifer E. Phillips-Cremins
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Structure of human chromatin-remodelling PBAF complex bound to a nucleosome
Cryo-electron microscopy structures of the 12-member PBAF complex provide insights into nucleosome recognition by the complex and the role of mutations in human disease.
- Junjie Yuan
- , Kangjing Chen
- & Zhucheng Chen
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| Open AccessNonlinear control of transcription through enhancer–promoter interactions
The transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship, and enhancer strength determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation.
- Jessica Zuin
- , Gregory Roth
- & Luca Giorgetti
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| Open AccessRixosomal RNA degradation contributes to silencing of Polycomb target genes
The rixosome associates with Polycomb repressive complexes and chromatin and has a role in silencing of Polycomb target gene expression in human cells via degradation of nascent RNA transcripts.
- Haining Zhou
- , Chad B. Stein
- & Danesh Moazed
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Brahma safeguards canalization of cardiac mesoderm differentiation
The BAF chromatin-remodelling complex ATPase gene Brm safeguards cell identity during directed cardiogenesis of mouse embryonic stem cells.
- Swetansu K. Hota
- , Kavitha S. Rao
- & Benoit G. Bruneau
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| Open AccessTargeting SWI/SNF ATPases in enhancer-addicted prostate cancer
PROTAC degrader–induced SWI/SNF inactivation abolishes DNA accessibility at enhancer elements of oncogenes and also tempers supra-physiologic expression of driver transcription factors, resulting in potent inhibition of tumour growth in mouse models.
- Lanbo Xiao
- , Abhijit Parolia
- & Arul M. Chinnaiyan
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Sex-specific chromatin remodelling safeguards transcription in germ cells
Following global DNA demethylation, mouse gonadal primordial germ cells undergo remodelling of repressive chromatin modifications, resulting in a sex-specific signature that is required to safeguard the transcriptional program.
- Tien-Chi Huang
- , Yi-Fang Wang
- & Petra Hajkova
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Activation of homologous recombination in G1 preserves centromeric integrity
Centromeres are able to recruit the homologous recombination machinery during G1 via CENP-A and HJURP, thereby preserving centromeric integrity even in the absence of a sister chromatid.
- Duygu Yilmaz
- , Audrey Furst
- & Evi Soutoglou
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| Open AccessGenome surveillance by HUSH-mediated silencing of intronless mobile elements
The human silencing hub (HUSH) complex uses introns to distinguish intronless foreign DNA from intron-containing host DNA and modifies chromatin to silence transcription of retrotransposons and retroviruses.
- Marta Seczynska
- , Stuart Bloor
- & Paul J. Lehner
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UTX condensation underlies its tumour-suppressive activity
Phase separation properties are a major determinant of UTX activity in chromatin regulation in tumour suppression, and are dependent on a core intrinsically disordered region of the protein.
- Bi Shi
- , Wei Li
- & Hao Jiang
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Mechanisms of BRCA1–BARD1 nucleosome recognition and ubiquitylation
The authors elucidate the mechanisms for the ubiquitylation specificity and recruitment of the ubiquitin ligase complex BRCA1–BARD1 to damaged DNA within chromatin to facilitate homologous recombination.
- Qi Hu
- , Maria Victoria Botuyan
- & Georges Mer
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BANP opens chromatin and activates CpG-island-regulated genes
BANP is identified as the transcription factor that binds the CGCG element in a DNA-methylation-dependent manner, opens chromatin and activates a class of essential CpG-island-regulated genes.
- Ralph S. Grand
- , Lukas Burger
- & Dirk Schübeler
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Phase separation drives aberrant chromatin looping and cancer development
The NUP98–HOXA9 oncogenic fusion protein found in leukaemia undergoes phase separation in the nucleus, which helps to promote activation of leukaemic genes and to establish aberrant chromatin looping.
- Jeong Hyun Ahn
- , Eric S. Davis
- & Gang Greg Wang
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Defining genome architecture at base-pair resolution
Micro Capture-C allows physical contacts to be determined at base-pair resolution, revealing that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters.
- Peng Hua
- , Mohsin Badat
- & James O. J. Davies
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Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity
A CRISPR–Cas9 screen of chromatin regulators in mouse tumour models treated with immune checkpoint blockade identifies SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity.
- Gabriel K. Griffin
- , Jingyi Wu
- & Bradley E. Bernstein
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| Open AccessHP1 drives de novo 3D genome reorganization in early Drosophila embryos
The heterochromatin protein HP1 has an essential role in establishing several features of the 3D nuclear organization of the genome during early embryonic development in Drosophila.
- Fides Zenk
- , Yinxiu Zhan
- & Nicola Iovino
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A high-resolution protein architecture of the budding yeast genome
A ChIP–exo method is used to define the genome-wide positional organization of proteins associated with gene transcription, DNA replication, centromeres, subtelomeres and transposons, revealing distinct protein assemblies for constitutive and inducible gene expression.
- Matthew J. Rossi
- , Prashant K. Kuntala
- & B. Franklin Pugh
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The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity
N6-methyladenosine RNA and its reader YTHDC1 serve as a bridge to silencing retrotransposons through the RNA derived from these retrotransposons in mouse ES cells.
- Jiadong Liu
- , Mingwei Gao
- & Jiekai Chen
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Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8
The meiotic proteins Spo11 and Rec8, which ensure meiotic recombination and reductional chromosome segregation, have additional activities that challenge centromere stability by promoting centromeric nucleosome remodelling in both fission yeast and human cells.
- Haitong Hou
- , Eftychia Kyriacou
- & Julia Promisel Cooper
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Loop extrusion as a mechanism for formation of DNA damage repair foci
During the repair of double-stranded DNA breaks, cohesin mediates the extrusion of loops of DNA along which phosphorylated H2AX spreads to establish a repair zone.
- Coline Arnould
- , Vincent Rocher
- & Gaëlle Legube
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Elevated NSD3 histone methylation activity drives squamous cell lung cancer
The histone H3K36 methyltransferase NSD3, which is associated with the common 8p11–12 chromosomal amplification, is an oncogenic driver in lung squamous cell carcinoma.
- Gang Yuan
- , Natasha M. Flores
- & Or Gozani
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Integrated spatial genomics reveals global architecture of single nuclei
Multiplexed imaging of 3,660 chromosomal loci in individual mouse embryonic stem cells by DNA seqFISH+ with immunofluorescence of 17 chromatin marks and subnuclear structures reveals invariant organization of loci within individual cells, and heterogeneous and long-lived distinct combinatorial chromatin states in cellular subpopulations.
- Yodai Takei
- , Jina Yun
- & Long Cai
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METTL3 regulates heterochromatin in mouse embryonic stem cells
Binding of METTL3 to chromatin is enriched over IAP family endogenous retroviral elements in mouse embryonic stem cells, helping to ensure the integrity of heterochromatin at these elements.
- Wenqi Xu
- , Jiahui Li
- & Hongjie Shen
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Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases
Cryo-electron microscopy structures of the nucleosome-bound NSD2 and NSD3 histone methyltransferases reveal the molecular basis of their histone modification activity, and show how mutations in these proteins can lead to oncogenesis.
- Wanqiu Li
- , Wei Tian
- & Zhanxin Wang
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Measuring DNA mechanics on the genome scale
A high-throughput, chromosome-wide analysis of DNA looping reveals its contribution to the organization of chromatin, and provides insight into how nucleosomes are deposited and organised de novo.
- Aakash Basu
- , Dmitriy G. Bobrovnikov
- & Taekjip Ha
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H1 histones control the epigenetic landscape by local chromatin compaction
Experiments using a conditional triple-knockout mouse strain show that histone H1 regulates the activity of chromatin domains by controlling chromatin compaction, genome architecture and histone methylation.
- Michael A. Willcockson
- , Sean E. Healton
- & Arthur I. Skoultchi
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Histone H1 loss drives lymphoma by disrupting 3D chromatin architecture
Mutations in histone H1 induce the remodelling of chromatin architecture to a more relaxed state, which leads to malignant transformation through changes in histone modifications and the expression of stem cell genes.
- Nevin Yusufova
- , Andreas Kloetgen
- & Ari M. Melnick
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A map of cis-regulatory elements and 3D genome structures in zebrafish
A comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin structure, the methylome and 3D genome organization in the zebrafish (Danio rerio) enables identification of species-specific and evolutionarily conserved regulatory features, and provides a foundation for modelling studies on human disease and development.
- Hongbo Yang
- , Yu Luan
- & Feng Yue