Article
|
Open Access
Featured
-
-
Article
| Open AccessLinker histone H1 and H3K56 acetylation are antagonistic regulators of nucleosome dynamics
The linker histone H1 is highly abundant and regulates DNA accessibility by compacting chromatin. Here the authors analyze transcription factor binding to nucleosomes and show that histone H1 suppresses unwrapping but does not directly block the binding of transcription factors.
- Morgan Bernier
- , Yi Luo
- & Michael G. Poirier
-
Article
| Open AccessHistone H1-mediated epigenetic regulation controls germline stem cell self-renewal by modulating H4K16 acetylation
Epigenetics plays critical roles in controlling stem cell self-renewal and differentiation. Here, Sun et al. show that H1 is intrinsically required in the regulation of germline stem cells in the Drosophilaovary by antagonizing MOF, a histone acetyltransferase specific for H4K16.
- Jin Sun
- , Hui-Min Wei
- & Jian-Quan Ni
-
Article
| Open AccessDiscovery of protein acetylation patterns by deconvolution of peptide isomer mass spectra
Deciphering patterns of histone modifications that modulate chromatin structure and function is important, but remains challenging. Here the authors describe a method to uncover patterns of site-specific histone acetylation by deconvolution of overlapping peptide isomer mass spectra.
- Nebiyu Abshiru
- , Olivier Caron-Lizotte
- & Pierre Thibault
-
Article
| Open AccessGeneration of a synthetic GlcNAcylated nucleosome reveals regulation of stability by H2A-Thr101 GlcNAcylation
Post-translational modification of histones has been implicated in gene regulation. Here, Lercher et al. generate synthetic GlcNAcylated histone 2A and nucleosomes and show that this modification can cause nucleosome destabilization, suggesting histone 2A O-GlcNAcylation may promote an open chromatin state and increase transcription.
- Lukas Lercher
- , Ritu Raj
- & Benjamin G. Davis
-
Article
| Open AccessLoss of lamin A function increases chromatin dynamics in the nuclear interior
Nuclear lamins mediate interactions between chromatin and the nuclear envelope, however they are also found throughout the nucleoplasm. By measuring the dynamics of different genomic loci, Bronshtein et al.show that lamin A is also required for the stability of the nuclear interior.
- I. Bronshtein
- , E. Kepten
- & Y. Garini
-
Article
| Open AccessSystematic chromatin state comparison of epigenomes associated with diverse properties including sex and tissue type
In contrast to genetic information, epigenetic state varies greatly under different conditions. Here, the authors develop ChromDiff and apply it to ENCODE and Roadmap Epigenomics datasets to find chromatin state differences associated with sex, tissue, and developmental age.
- Angela Yen
- & Manolis Kellis
-
Article
| Open AccessThe chromatin remodeller RSF1 is essential for PLK1 deposition and function at mitotic kinetochores
Polo-like kinase 1 (PLK1) is recruited to kinetochores during mitosis, where it is required for proper chromosome alignment. Leeet al. show that the chromatin-remodelling factor RSF1 is required for PLK1 recruitment, and that this function depends on phosphorylation of RSF1 by the mitotic kinase CDK1.
- Ho-Soo Lee
- , Yong-Yea Park
- & Hyeseong Cho
-
Article
| Open AccessMEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures
Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin. Here, the authors show that lncRNA MEG3regulates the TGF-β pathway by bridging the interactions between polycomb repressive complex 2 and the distal regulatory elements of the TGF-β pathway genes via formation of RNA–DNA triplexes.
- Tanmoy Mondal
- , Santhilal Subhash
- & Chandrasekhar Kanduri
-
Article
| Open AccessHighly condensed chromatins are formed adjacent to subtelomeric and decondensed silent chromatin in fission yeast
The level of chromatin condensation and gene expression is believed to be inversely correlated. Here the authors show that the transcriptionally silent telomere regions are flanked by highly condensed chromatin, and are less condensed than euchromatin in the interphase of Schizosaccharomyces pombe.
- Atsushi Matsuda
- , Yuji Chikashige
- & Yasushi Hiraoka
-
Article
| Open AccessSuppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX
ATRX, a chromatin remodelling factor, is mutated in cancers that maintain telomere length by alternative lengthening of telomeres (ALT). Here, the authors show that ectopic expression of ATRX triggers telomere shortening, ALT suppression and reduced replication fork stalling.
- David Clynes
- , Clare Jelinska
- & Richard J. Gibbons
-
Article
| Open AccessSCARECROW-LIKE15 interacts with HISTONE DEACETYLASE19 and is essential for repressing the seed maturation programme
Epigenetic regulation is critical for controlling gene expression during the transition from embryo to seedling in plants. Here Gao et al. report that in Arabidopsis, the SCARECROW-LIKE15 protein physically interacts with a histone deacetylase to repress expression of embryonic traits in seedlings.
- Ming-Jun Gao
- , Xiang Li
- & Dwayne D. Hegedus
-
Article |
TRIM29 regulates the assembly of DNA repair proteins into damaged chromatin
Many proteins are assembled into damaged chromatins to repair DNA double-strand breaks (DSBs). Here, the authors show that TRIM29 binds to modified histone H3 and H4 tails following DSB formation and functions as a scaffold protein to assemble DNA repair proteins into chromatin.
- Yasushi Masuda
- , Hidehisa Takahashi
- & Shigetsugu Hatakeyama
-
Article
| Open AccessMultivalency governs HP1α association dynamics with the silent chromatin state
Chromatin effector proteins often employ multivalent interactions with histone post-translational modifications. Here by using chemically defined nucleosome array and single-molecule microscopy, the authors show that effector multivalency prolongs chromatin retention and accelerates the association rate.
- Sinan Kilic
- , Andreas L. Bachmann
- & Beat Fierz
-
Article |
Opposing calcium-dependent signalling pathways control skeletal muscle differentiation by regulating a chromatin remodelling enzyme
Brg1 is part of the SWI/SNF chromatin remodelling complex that is essential for embryonic development. Here, the authors show that Brg1 is the target of two opposing calcium-regulated molecules involved in myogenesis: calcineurin, which promotes myogenesis, and protein kinase C β (PKCβ), which inhibits it.
- Brian T. Nasipak
- , Teresita Padilla-Benavides
- & Anthony N. Imbalzano
-
Article
| Open AccessProgrammed cell death 5 mediates HDAC3 decay to promote genotoxic stress response
The tumour suppressor p53 is known to be inhibited by histone deacetylase 3 but the molecular mechanism is poorly understood. Here Choi et al. show regulation by programmed cell death 5 and an essential role in activating p53 following DNA damage.
- Hyo-Kyoung Choi
- , Youngsok Choi
- & Ho-Geun Yoon
-
Article
| Open AccessThe tethering of chromatin to the nuclear envelope supports nuclear mechanics
The mechanical properties of the metazoan nucleus can be influenced by the nuclear lamina. Here, Schreiner et al.show that untethering chromatin from the inner nuclear membrane results in highly deformable, softer nuclei, revealing an important role for chromatin in modulating nuclear mechanics.
- Sarah M. Schreiner
- , Peter K. Koo
- & Megan C. King
-
Article |
Structural analyses of the chromatin remodelling enzymes INO80-C and SWR-C
INO80-C and SWR-C are chromatin remodelling enzymes with roles in transcription pathways. Here, the authors show that they both have similar architectures displaying a ‘tail’ domain and a heterohexameric ‘head’ domain, with conformational changes influencing nucleosomal binding and enzyme activity.
- Shinya Watanabe
- , Dongyan Tan
- & Craig L. Peterson
-
Article
| Open AccessJMJD1A is a signal-sensing scaffold that regulates acute chromatin dynamics via SWI/SNF association for thermogenesis
Demethylase JMJD1A activates thermogenesis-related target genes in response to β-adrenergic hormones. Here, the authors show that phosphorylation of JMJD1A at S265 increases its interaction with the SWI/SNF chromatin remodeler, leading to long-range chromatin interactions and target gene activation.
- Yohei Abe
- , Royhan Rozqie
- & Juro Sakai
-
Article |
Transcriptional activation by the thyroid hormone receptor through ligand-dependent receptor recruitment and chromatin remodelling
The bimodal switch model posits that the unliganded thyroid hormone receptor (TR) binds chromatin stably. Here, the authors demonstrate ligand dependent recruitment of TR to chromatin, and further show that both unliganded and ligand-bound TR engages with chromatin in a highly dynamic manner.
- Lars Grøntved
- , Joshua J. Waterfall
- & Sheue-yann Cheng
-
Article |
Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3
The chemical honokiol is found in the bark of magnolia trees, which are used for traditional medicine in Asian countries. Here, Pillai et al, show honokiol protects the heart from hypertrophic remodelling in mice, and even reverses established cardiac hypertrophy, by activating the deacetylase Sirt3.
- Vinodkumar B. Pillai
- , Sadhana Samant
- & Mahesh P. Gupta
-
Article
| Open AccessPontin functions as an essential coactivator for Oct4-dependent lincRNA expression in mouse embryonic stem cells
Long non-coding RNAs or lincRNAs identified in embryonic stem (ES) cells have been shown to regulate ES cell states; however, how these lincRNAs are regulated remains unclear. Here the authors show that the transcriptional coactivator Pontin regulates the expression of lincRNAs involved in ES cell maintenance in an Oct4-dependent manner.
- Kyungjin Boo
- , Jinhyuk Bhin
- & Sung Hee Baek
-
Article |
A cohesin–OCT4 complex mediates Sox enhancers to prime an early embryonic lineage
Higher order chromatin structures affect gene transcription, but how they determine cell fate is unclear. Here, the authors show that OCT4 and SALL4 alter the higher-order chromatin structure and mediate cell fate switching in embryonic cells by targeting cohesin and polycomb complexes, respectively.
- Nesrine Abboud
- , Thomas Moore- Morris
- & Michel Pucéat
-
Article
| Open AccessEnd-targeting proteomics of isolated chromatin segments of a mammalian ribosomal RNA gene promoter
The identification of factors involved in eukaryotic DNA regulation at specific genomic regions distinct technical challenges. Here, the authors describe ePICh, a method that allows for the efficient isolation of chromatin factors associated with complex low abundance targets within the large genome of mammalian cells.
- Satoru Ide
- & Jerome Dejardin
-
Article
| Open AccessSINE transcription by RNA polymerase III is suppressed by histone methylation but not by DNA methylation
Transcription of short interspersed nuclear elements (SINEs) allows retrotransposition that contributes to chromosomal instability. Here, the authors show that methylation of histones, rather than DNA, plays a dominant role in suppressing SINE expression.
- Dhaval Varshney
- , Jana Vavrova-Anderson
- & Robert J. White
-
Article
| Open AccessChromatin organization at the nuclear pore favours HIV replication
Retroviruses such as HIV integrate into the host genome as an essential step prior to their replication. Here Lelek et al. identify nuclear pore complex proteins that are essential for HIV nuclear import and productive integration, and show that the intranuclear protein Tpr influences integration into transcriptionally active chromatin.
- Mickaël Lelek
- , Nicoletta Casartelli
- & Francesca Di Nunzio
-
Article
| Open AccessCapture Hi-C identifies the chromatin interactome of colorectal cancer risk loci
Multiple regulatory elements distant from their targets on the linear genome can influence gene expression through chromatin looping. Here, the authors report an improved chromosome conformation capture approach that can be used to identify long-range chromatin interactions in cancer risk loci.
- Roland Jäger
- , Gabriele Migliorini
- & Richard S. Houlston
-
Article |
Histone demethylase KDM5A is regulated by its reader domain through a positive-feedback mechanism
Histone lysine methylation plays crucial roles in controlling gene expression. Here the authors demonstrate that the activity of the histone lysine demethylase KDM5A is regulated through a feedback mechanism involving communication between the histone tail-binding and catalytic domains.
- Idelisse Ortiz Torres
- , Kristopher M. Kuchenbecker
- & Danica Galonić Fujimori
-
Article |
ZNF143 provides sequence specificity to secure chromatin interactions at gene promoters
Chromatin interactions can connect distal regulatory elements to promoters via protein factors, but few such factors have been identified. Here, the authors show that zinc-finger protein ZNF143 is a sequence-specific chromatin-looping factor that connects promoters with distal regulatory elements.
- Swneke D. Bailey
- , Xiaoyang Zhang
- & Mathieu Lupien
-
Article |
Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils
How IL-6 expression is regulated in human neutrophils has remained unclear. Here the authors show, using highly purified neutrophils, that TLR8 or TLR4 signalling activates latent enhancers and cooperates with autocrine TNFα to induce IL-6transcription.
- Maili Zimmermann
- , Francisco Bianchetto Aguilera
- & Marco A. Cassatella
-
Article |
Chromatin decompaction by the nucleosomal binding protein HMGN5 impairs nuclear sturdiness
Whether heterochromatin affects the physical properties of the nucleus is not known. Here, Furusawa et al. show that chromatin decompaction decreases the sturdiness of the nucleus in cultured cells and leads to lamina disruption and cardiac abnormalities in adult mice, suggesting a structural, non-genetic function for heterochromatin.
- Takashi Furusawa
- , Mark Rochman
- & Michael Bustin
-
Article |
A chromatin activity-based chemoproteomic approach reveals a transcriptional repressome for gene-specific silencing
Immune cell pro-inflammatory gene expression is suppressed following prolonged stimulation. Using a chemoproteomic approach, the authors show that methyltransferase G9a forms a protein complex that promotes the transcriptional repressor activity of c-Myc to repress inflammation-induced gene expression.
- Cui Liu
- , Yanbao Yu
- & Xian Chen
-
Article
| Open AccessCritical role of lysine 134 methylation on histone H2AX for γ-H2AX production and DNA repair
γ-H2AX The Ser139 phosphorylated form of H2AX, γ-H2AX, is generated in response to DNA double-strand breaks and is involved in the repair process. Here, Sone et al.show that H2AX K134 methylation by SUV39H2 is crucial for the production of γ-H2AX, and that loss of methylation correlates with radio- and chemosensitivity.
- Kenbun Sone
- , Lianhua Piao
- & Ryuji Hamamoto
-
Article |
Histone H3.3 and its proteolytically processed form drive a cellular senescence programme
Cellular senescence involves extensive structural changes to chromatin, but the role of histone variants and histone cleavage is unknown. Here, Duarte et al.identify histone variant H3.3 and its proteolytically processed form lacking a portion of the N-terminal tail as key regulators of senescence.
- Luis F. Duarte
- , Andrew R. J. Young
- & Emily Bernstein
-
Article
| Open AccessGenomic analyses of gynaecologic carcinosarcomas reveal frequent mutations in chromatin remodelling genes
Malignant mixed Müllerian tumours are a rare and aggressive gynaecological cancer with poor 5-year survival rates. Here, the authors characterize the mutational landscape of carcinosarcomas and highlight the role of chromatin remodelling dysregulation in carcinosarcoma tumorigenesis.
- Siân Jones
- , Nicolas Stransky
- & Victor E. Velculescu
-
Article |
Improved nucleosome-positioning algorithm iNPS for accurate nucleosome positioning from sequencing data
Changes in nucleosome positioning often underlie the reprogramming of gene expression during differentiation. Here Chen et al. describe a novel algorithm - iNPS - that outperforms current methods in accurately determine nucleosome position genome-wide.
- Weizhong Chen
- , Yi Liu
- & Jing-Dong Jackie Han
-
Article |
Solution-state conformation and stoichiometry of yeast Sir3 heterochromatin fibres
Heterochromatin is a ‘repressed’ chromatin state involved in the generation of centromeres, the protection of telomeres and the maintenance of genome integrity. Here Swygert et al.show that Sir3 - a key factor in the formation of heterochromatin - promotes a chromatin structure distinct from the canonical 30 nm fibre.
- Sarah G. Swygert
- , Benjamin J. Manning
- & Craig L. Peterson
-
Article
| Open AccessNucleosomal occupancy changes locally over key regulatory regions during cell differentiation and reprogramming
Changes in chromatin structure impact gene expression programs by modulating accessibility to the transcription machinery. Here, West et al. explore differences in nucleosome occupancy between mammalian pluripotent and somatic cells and uncover regulatory regions likely to play key roles in determining cell identity.
- Jason A. West
- , April Cook
- & Robert E. Kingston
-
Article
| Open AccessInvertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon
The process of controlled chromatin release from the nuclei of inflammatory cells to entrap and kill bacteria, termed ETosis, is important in innate immunity in vertebrates. Here the authors demonstrate that ETosis, mediated by hematocytes, also contributes to defence mechanisms in invertebrates.
- Calum T. Robb
- , Elisabeth A. Dyrynda
- & Valerie J. Smith
-
Article
| Open AccessO-GlcNAc-mediated interaction between VER2 and TaGRP2 elicits TaVRN1 mRNA accumulation during vernalization in winter wheat
In temperate cereals such as winter wheat, prolonged periods of cold induce upregulation of TaVRN1 to control the timing of seasonal flowering. Xiao et al. show TaVRN1 mRNA accumulation is regulated by O-GlcNAc modification of the RNA-binding protein TaGRP2, which increases progressively in response to cold.
- Jun Xiao
- , Shujuan Xu
- & Kang Chong
-
Article |
Loss of neuronal 3D chromatin organization causes transcriptional and behavioural deficits related to serotonergic dysfunction
It is becoming increasingly clear that the three-dimensional organization of chromatin within the nucleus plays a role in regulating gene expression. Here, Ito et al.demonstrate that the disruption of chromocenter clustering in mature neuronal cells results in specific transcriptional and behavioural defects in mice.
- Satomi Ito
- , Adriana Magalska
- & Angel Barco
-
Article |
Chd5 orchestrates chromatin remodelling during sperm development
Somatic histones are replaced with sperm-specific basic proteins, called protamines, during the chromatin remodelling phase of spermatogenesis. Here, the authors show that the chromatin remodelling protein Chd5 is required for histone-to-protamine replacement during spermatogenesis in mice.
- Wangzhi Li
- , Jie Wu
- & Alea A. Mills
-
Article |
The 19S proteasome subunit Rpt3 regulates distribution of CENP-A by associating with centromeric chromatin
The histone variant CENP-A has a crucial role in defining centromeric chromatin and is required for accurate segregation of chromosomes during mitosis. Here, Kitagawa et al.identify Rpt3, a subunit of the 19S proteasome, as a novel factor regulating CENP localization.
- Teppei Kitagawa
- , Kojiro Ishii
- & Tomohiro Matsumoto
-
Article
| Open AccessThe nucleosome acidic patch plays a critical role in RNF168-dependent ubiquitination of histone H2A
The E3 ubiquitin ligase RNF168 ubiquitinates specific lysines on histone H2A as part of the DNA damage response. Here, the authors show that the acidic patch on the histone H2A/H2B dimer catalyses RNF168-dependent ubiquitination of histone 2A by redirecting ubiquitination activity towards the relevant target lysines.
- Francesca Mattiroli
- , Michael Uckelmann
- & Titia K. Sixma
-
Article |
Binding of PHF1 Tudor to H3K36me3 enhances nucleosome accessibility
Binding of the Tudor domain of the PHD finger protein PHF1 to H3K36me3 inhibits Polycomb PRC2 complex methyltransferase activity. Here, Musselman et al.characterize this interaction in the context of the full nucleosome and show dual binding of the PHF1 Tudor domain to H3K36me3 and double-stranded DNA.
- Catherine A. Musselman
- , Matthew D. Gibson
- & Tatiana G. Kutateladze
-
Article |
Stepwise histone modifications are mediated by multiple enzymes that rapidly associate with nascent DNA during replication
Chromatin marks have to be re-established after DNA replication. Here Petruk et al. show that many histone-modifying enzymes are found in close proximity to newly replicated DNA in cells of Drosophilaembryos before the corresponding histone marks are re-established.
- Svetlana Petruk
- , Kathryn L. Black
- & Alexander Mazo
-
Article |
Semiconductor-based DNA sequencing of histone modification states
Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.
- Christine S. Cheng
- , Kunal Rai
- & Ido Amit
-
Article |
Torque modulates nucleosome stability and facilitates H2A/H2B dimer loss
Histone H2A-H2B heterodimers are lost from nucleosomes during transcription by RNA polymerase II. Here Sheinin et al. investigate the behaviour of single nucleosomes subjected to DNA supercoiling and observe a loss of these heterodimers under positive supercoiling, which might have implications for histone turnover during transcription in vivo.
- Maxim Y. Sheinin
- , Ming Li
- & Michelle D. Wang
-
Article |
MacroH2A histone variants act as a barrier upon reprogramming towards pluripotency
Chromatin templates can act as barriers against cellular reprogramming. Gaspar-Maia and colleagues use mouse models deficient in the histone variants macroH2A1 and macroH2A2, and find that macroH2A functions as an epigenetic barrier against induced pluripotency by silencing Utx target genes.
- Alexandre Gaspar-Maia
- , Zulekha A. Qadeer
- & Emily Bernstein
-
Article |
Dynamic histone marks in the hippocampus and cortex facilitate memory consolidation
Changes in gene expression in the hippocampus and the cortex are pivotal for memory consolidation. Gräff and colleagues use a recognition task in mice to show that epigenetic post-translational modifications are rapidly activated in the hippocampus after learning, but induced with a delay in the cortex.
- Johannes Gräff
- , Bisrat T. Woldemichael
- & Isabelle M. Mansuy