Articles

Genomic imprinting does not reduce the dosage of UBE3A in neurons

The ubiquitin protein E3A ligase gene (UBE3A) gene is imprinted with maternal-specific expression in neurons and biallelically expressed in all other cell types. Both loss-of-function and gain-of-function mutatio...

Authors: Paul R. Hillman, Sarah G. B. Christian, Ryan Doan, Noah D. Cohen, Kranti Konganti, Kory Douglas, Xu Wang, Paul B. Samollow and Scott V. Dindot

A computational approach for the functional classification of the epigenome

In the last decade, advanced functional genomics approaches and deep sequencing have allowed large-scale mapping of histone modifications and other epigenetic marks, highlighting functional relationships betw...

Authors: Francesco Gandolfi and Anna Tramontano

Transcription and chromatin determinants of de novo DNA methylation timing in oocytes

Gametogenesis in mammals entails profound re-patterning of the epigenome. In the female germline, DNA methylation is acquired late in oogenesis from an essentially unmethylated baseline and is established larg...

Authors: Lenka Gahurova, Shin-ichi Tomizawa, Sébastien A. Smallwood, Kathleen R. Stewart-Morgan, Heba Saadeh, Jeesun Kim, Simon R. Andrews, Taiping Chen and Gavin Kelsey

Stabilization of Foxp3 expression by CRISPR-dCas9-based epigenome editing in mouse primary T cells

Epigenome editing is expected to manipulate transcription and cell fates and to elucidate the gene expression mechanisms in various cell types. For functional epigenome editing, assessing the chromatin context...

Authors: Masahiro Okada, Mitsuhiro Kanamori, Kazue Someya, Hiroko Nakatsukasa and Akihiko Yoshimura

DNA methylation and DNA methyltransferases

The prevailing views as to the form, function, and regulation of genomic methylation patterns have their origin many years in the past, at a time when the structure of the mammalian genome was only dimly perce...

Authors: John R. Edwards, Olya Yarychkivska, Mathieu Boulard and Timothy H. Bestor

Differential DNA methylation and lymphocyte proportions in a Costa Rican high longevity region

The Nicoya Peninsula in Costa Rica has one of the highest old-age life expectancies in the world, but the underlying biological mechanisms of this longevity are not well understood. As DNA methylation is hypot...

Authors: Lisa M. McEwen, Alexander M. Morin, Rachel D. Edgar, Julia L. MacIsaac, Meaghan J. Jones, William H. Dow, Luis Rosero-Bixby, Michael S. Kobor and David H. Rehkopf

Comprehensive evaluation of genome-wide 5-hydroxymethylcytosine profiling approaches in human DNA

The discovery that 5-methylcytosine (5mC) can be oxidized to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation (TET) proteins has prompted wide interest in the potential role of 5hmC in reshaping ...

Authors: Ksenia Skvortsova, Elena Zotenko, Phuc-Loi Luu, Cathryn M. Gould, Shalima S. Nair, Susan J. Clark and Clare Stirzaker

Differential DNA methylation at conserved non-genic elements and evidence for transgenerational inheritance following developmental exposure to mono(2-ethylhexyl) phthalate and 5-azacytidine in zebrafish

Exposure to environmental stressors during development may lead to latent and transgenerational adverse health effects. To understand the role of DNA methylation in these effects, we used zebrafish as a verteb...

Authors: Jorke H. Kamstra, Liana Bastos Sales, Peter Aleström and Juliette Legler

Fetal testis organ culture reproduces the dynamics of epigenetic reprogramming in rat gonocytes

Epigenetic reprogramming is a critical step in male germ cell development that occurs during perinatal life. It is characterized by the remodeling of different epigenetic marks such as DNA methylation (5mC) an...

Authors: Arlette Rwigemera, Fabien Joao and Geraldine Delbes

Links between DNA methylation and nucleosome occupancy in the human genome

DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator o...

Authors: Clayton K. Collings and John N. Anderson

Internal modifications in the CENP-A nucleosome modulate centromeric dynamics

Posttranslational modifications of core histones are correlated with changes in transcriptional status, chromatin fiber folding, and nucleosome dynamics. However, within the centromere-specific histone H3 vari...

Authors: Minh Bui, Mary Pitman, Arthur Nuccio, Serene Roque, Paul Gregory Donlin-Asp, Aleksandra Nita-Lazar, Garegin A. Papoian and Yamini Dalal

Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes

Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that th...

Authors: Arnab Nayak, Anja Reck, Christian Morsczeck and Stefan Müller

Well-positioned nucleosomes punctuate polycistronic pol II transcription units and flank silent VSG gene arrays in Trypanosoma brucei

The compaction of DNA in chromatin in eukaryotes allowed the expansion of genome size and coincided with significant evolutionary diversification. However, chromatin generally represses DNA function, and mecha...

Authors: Johannes Petrus Maree, Megan Lindsay Povelones, David Johannes Clark, Gloria Rudenko and Hugh-George Patterton

Dynamics of 5-methylcytosine and 5-hydroxymethylcytosine during pronuclear development in equine zygotes produced by ICSI

Global epigenetic reprogramming is considered to be essential during embryo development to establish totipotency. In the classic model first described in the mouse, the genome-wide DNA demethylation is asymmet...

Authors: Sonia Heras, Katrien Smits, Catharina De Schauwer and Ann Van Soom

Histone peptide microarray screen of chromo and Tudor domains defines new histone lysine methylation interactions

Histone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized “reader” domains. Despite effor...

Authors: Erin K. Shanle, Stephen A. Shinsky, Joseph B. Bridgers, Narkhyun Bae, Cari Sagum, Krzysztof Krajewski, Scott B. Rothbart, Mark T. Bedford and Brian D. Strahl

Silencing markers are retained on pericentric heterochromatin during murine primordial germ cell development

In the nuclei of most mammalian cells, pericentric heterochromatin is characterized by DNA methylation, histone modifications such as H3K9me3 and H4K20me3, and specific binding proteins like heterochromatin-bi...

Authors: Aristea Magaraki, Godfried van der Heijden, Esther Sleddens-Linkels, Leonidas Magarakis, Wiggert A. van Cappellen, Antoine H. F. M. Peters, Joost Gribnau, Willy M. Baarends and Maureen Eijpe

Identification of epigenetic signature associated with alpha thalassemia/mental retardation X-linked syndrome

Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX. The mechanisms involved in the ATR-X pathology are not completely understood, but may i...

Authors: Laila C. Schenkel, Kristin D. Kernohan, Arran McBride, Ditta Reina, Amanda Hodge, Peter J. Ainsworth, David I. Rodenhiser, Guillaume Pare, Nathalie G. Bérubé, Cindy Skinner, Kym M. Boycott, Charles Schwartz and Bekim Sadikovic

Assessing histone demethylase inhibitors in cells: lessons learned

Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The ...

Authors: Stephanie B. Hatch, Clarence Yapp, Raquel C. Montenegro, Pavel Savitsky, Vicki Gamble, Anthony Tumber, Gian Filippo Ruda, Vassilios Bavetsias, Oleg Fedorov, Butrus Atrash, Florence Raynaud, Rachel Lanigan, LeAnne Carmichael, Kathy Tomlin, Rosemary Burke, Susan M. Westaway…

SMYD5 regulates H4K20me3-marked heterochromatin to safeguard ES cell self-renewal and prevent spurious differentiation

Epigenetic regulation of chromatin states is thought to control the self-renewal and differentiation of embryonic stem (ES) cells. However, the roles of repressive histone modifications such as trimethylated h...

Authors: Benjamin L. Kidder, Gangqing Hu, Kairong Cui and Keji Zhao

PRC2 is required for extensive reorganization of H3K27me3 during epigenetic reprogramming in mouse fetal germ cells

Defining how epigenetic information is established in the germline during fetal development is key to understanding how epigenetic information is inherited and impacts on evolution and human health and disease.

Authors: Lexie Prokopuk, Jessica M. Stringer, Kirsten Hogg, Kirstin D. Elgass and Patrick S. Western

Decoupling the downstream effects of germline nuclear RNAi reveals that H3K9me3 is dispensable for heritable RNAi and the maintenance of endogenous siRNA-mediated transcriptional silencing in Caenorhabditis elegans

Germline nuclear RNAi in C. elegans is a transgenerational gene-silencing pathway that leads to H3K9 trimethylation (H3K9me3) and transcriptional silencing at the target genes. H3K9me3 induced by either exogenous...

Authors: Natallia Kalinava, Julie Zhouli Ni, Kimberly Peterman, Esteban Chen and Sam Guoping Gu

Histone and DNA methylation control by H3 serine 10/threonine 11 phosphorylation in the mouse zygote

In the mammalian zygote, epigenetic reprogramming is a tightly controlled process of coordinated alterations of histone and DNA modifications. The parental genomes of the zygote show distinct patterns of hist...

Authors: Jie Lan, Konstantin Lepikhov, Pascal Giehr and Joern Walter

In utero exposure to maternal smoking is associated with DNA methylation alterations and reduced neuronal content in the developing fetal brain

Intrauterine exposure to maternal smoking is linked to impaired executive function and behavioral problems in the offspring. Maternal smoking is associated with reduced fetal brain growth and smaller volume of...

Authors: Zac Chatterton, Brigham J. Hartley, Man-Ho Seok, Natalia Mendelev, Sean Chen, Maria Milekic, Gorazd Rosoklija, Aleksandar Stankov, Iskra Trencevsja-Ivanovska, Kristen Brennand, Yongchao Ge, Andrew J. Dwork and Fatemeh Haghighi

Sex-specific chromatin landscapes in an ultra-compact chordate genome

In multicellular organisms, epigenome dynamics are associated with transitions in the cell cycle, development, germline specification, gametogenesis and inheritance. Evolutionarily, regulatory space has increa...

Authors: Pavla Navratilova, Gemma Barbara Danks, Abby Long, Stephen Butcher, John Robert Manak and Eric M. Thompson

MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones

Histones and histone variants are essential components of the nuclear chromatin. While mass spectrometry has opened a large window to their characterization and functional studies, their identification from pr...

Authors: Sara El Kennani, Annie Adrait, Alexey K. Shaytan, Saadi Khochbin, Christophe Bruley, Anna R. Panchenko, David Landsman, Delphine Pflieger and Jérôme Govin

Genome-wide methylation data mirror ancestry information

Genetic data are known to harbor information about human demographics, and genotyping data are commonly used for capturing ancestry information by leveraging genome-wide differences between populations. In con...

Authors: Elior Rahmani, Liat Shenhav, Regev Schweiger, Paul Yousefi, Karen Huen, Brenda Eskenazi, Celeste Eng, Scott Huntsman, Donglei Hu, Joshua Galanter, Sam S. Oh, Melanie Waldenberger, Konstantin Strauch, Harald Grallert, Thomas Meitinger, Christian Gieger…

The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes

The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function—the storage, expression, and replication of genetic information—is still one of the central i...

Authors: Tobias A. Knoch, Malte Wachsmuth, Nick Kepper, Michael Lesnussa, Anis Abuseiris, A. M. Ali Imam, Petros Kolovos, Jessica Zuin, Christel E. M. Kockx, Rutger W. W. Brouwer, Harmen J. G. van de Werken, Wilfred F. J. van IJcken, Kerstin S. Wendt and Frank G. Grosveld

Dynamic properties of independent chromatin domains measured by correlation spectroscopy in living cells

Genome organization into subchromosomal topologically associating domains (TADs) is linked to cell-type-specific gene expression programs. However, dynamic properties of such domains remain elusive, and it is ...

Authors: Malte Wachsmuth, Tobias A. Knoch and Karsten Rippe

“Gap hunting” to characterize clustered probe signals in Illumina methylation array data

The Illumina 450k array has been widely used in epigenetic association studies. Current quality-control (QC) pipelines typically remove certain sets of probes, such as those containing a SNP or with multiple m...

Authors: Shan V. Andrews, Christine Ladd-Acosta, Andrew P. Feinberg, Kasper D. Hansen and M. Daniele Fallin

Targeted bisulfite sequencing of the dynamic DNA methylome

The ability to measure DNA methylation precisely and efficiently continues to drive our understanding of this modification in development and disease. Whole genome bisulfite sequencing has the advantage of the...

Authors: Michael J. Ziller, Elena K. Stamenova, Hongcang Gu, Andreas Gnirke and Alexander Meissner

HOXA repression is mediated by nucleoporin Nup93 assisted by its interactors Nup188 and Nup205

The nuclear pore complex (NPC) mediates nuclear transport of RNA and proteins into and out of the nucleus. Certain nucleoporins have additional functions in chromatin organization and transcription regulation....

Authors: Ajay S. Labade, Krishanpal Karmodiya and Kundan Sengupta

Widespread recovery of methylation at gametic imprints in hypomethylated mouse stem cells following rescue with DNMT3A2

Imprinted loci are paradigms of epigenetic regulation and are associated with a number of genetic disorders in human. A key characteristic of imprints is the presence of a gametic differentially methylated reg...

Authors: Avinash Thakur, Sarah-Jayne Mackin, Rachelle E. Irwin, Karla M. O’Neill, Gareth Pollin and Colum Walsh

Protein kinase Msk1 physically and functionally interacts with the KMT2A/MLL1 methyltransferase complex and contributes to the regulation of multiple target genes

The KMT2A/MLL1 lysine methyltransferase complex is an epigenetic regulator of selected developmental genes, in part through the SET domain-catalysed methylation of H3K4. It is essential for normal embryonic de...

Authors: Maaike Wiersma, Marianne Bussiere, John A. Halsall, Nil Turan, Robert Slany, Bryan M. Turner and Karl P. Nightingale

Insights into long noncoding RNAs of naked mole rat (Heterocephalus glaber) and their potential association with cancer resistance

Long noncoding RNAs (lncRNAs) are a class of ubiquitous noncoding RNAs and have been found to act as tumor suppressors or oncogenes, which dramatically altered our understanding of cancer. Naked mole rat (NMR, He...

Authors: Jian-Jun Jiang, Le-Hua Cheng, Huan Wu, Yong-Han He and Qing-Peng Kong

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understandin...

Authors: Suhn Kyong Rhie, Yu Guo, Yu Gyoung Tak, Lijing Yao, Hui Shen, Gerhard A. Coetzee, Peter W. Laird and Peggy J. Farnham

Systematic comparison of monoclonal versus polyclonal antibodies for mapping histone modifications by ChIP-seq

The robustness of ChIP-seq datasets is highly dependent upon the antibodies used. Currently, polyclonal antibodies are the standard despite several limitations: They are non-renewable, vary in performance betw...

Authors: Michele Busby, Catherine Xue, Catherine Li, Yossi Farjoun, Elizabeth Gienger, Ido Yofe, Adrianne Gladden, Charles B. Epstein, Evan M. Cornett, Scott B. Rothbart, Chad Nusbaum and Alon Goren

Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia

A comprehensive assessment of the epigenetic dynamics in cancer cells is the key to understanding the molecular mechanisms underlying cancer and to improving cancer diagnostics, prognostics and treatment. By c...

Authors: Michiel E. Adriaens, Peggy Prickaerts, Michelle Chan-Seng-Yue, Twan van den Beucken, Vivian E. H. Dahlmans, Lars M. Eijssen, Timothy Beck, Bradly G. Wouters, Jan Willem Voncken and Chris T. A. Evelo

Expression and epigenomic landscape of the sex chromosomes in mouse post-meiotic male germ cells

During meiosis, the X and Y chromosomes are transcriptionally silenced. The persistence of repressive chromatin marks on the sex chromatin after meiosis initially led to the assumption that XY gene silencing ...

Authors: Charlotte Moretti, Daniel Vaiman, Frederic Tores and Julie Cocquet

Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3

Trimethylation at histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) controls gene activity during development and differentiation. Whether H3K4me3 and H3K27me3 changes dynamically in response to altered m...

Authors: Peggy Prickaerts, Michiel E. Adriaens, Twan van den Beucken, Elizabeth Koch, Ludwig Dubois, Vivian E. H. Dahlmans, Caroline Gits, Chris T. A. Evelo, Michelle Chan-Seng-Yue, Bradly G. Wouters and Jan Willem Voncken

Histone macroH2A1.2 promotes metabolic health and leanness by inhibiting adipogenesis

Obesity has tremendous impact on the health systems. Its epigenetic bases are unclear. MacroH2A1 is a variant of histone H2A, present in two alternatively exon-spliced isoforms macroH2A1.1 and macroH2A1.2, reg...

Authors: Valerio Pazienza, Concetta Panebianco, Francesca Rappa, Domenico Memoli, Michela Borghesan, Sara Cannito, Asami Oji, Giuseppe Mazza, Domenico Tamburrino, Giuseppe Fusai, Rosario Barone, Giulia Bolasco, Francesc Villarroya, Joan Villarroya, Kiyotaka Hatsuzawa, Francesco Cappello…

An H4K16 histone acetyltransferase mediates decondensation of the X chromosome in C. elegans males

In C. elegans, in order to equalize gene expression between the sexes and balance X and autosomal expression, two steps are believed to be required. First, an unknown mechanism is hypothesized to upregulate the X...

Authors: Alyssa C. Lau, Kevin P. Zhu, Elizabeth A. Brouhard, Michael B. Davis and Györgyi Csankovszki

High-throughput assessment of context-dependent effects of chromatin proteins

Chromatin proteins control gene activity in a concerted manner. We developed a high-throughput assay to study the effects of the local chromatin environment on the regulatory activity of a protein of interest....

Authors: Laura Brueckner, Joris van Arensbergen, Waseem Akhtar, Ludo Pagie and Bas van Steensel

EpiMINE, a computational program for mining epigenomic data

In epigenetic research, both the increasing ease of high-throughput sequencing and a greater interest in genome-wide studies have resulted in an exponential flooding of epigenetic-related data in public domai...

Authors: SriGanesh Jammula and Diego Pasini

Imprinted DNA methylation reconstituted at a non-imprinted locus

In mammals, tight regulation of cytosine methylation is required for embryonic development and cellular differentiation. The trans-acting DNA methyltransferases that catalyze this modification have been identifi...

Authors: David H. Taylor, Chelsea M. McLean, Warren L. Wu, Alex B. Wang and Paul D. Soloway

Nucleosome distortion as a possible mechanism of transcription activation domain function

After more than three decades since the discovery of transcription activation domains (ADs) in gene-specific activators, the mechanism of their function remains enigmatic. The widely accepted model of direct r...

Authors: Tamara Y. Erkina and Alexandre M. Erkine

Fine-tuning of chromatin composition and Polycomb recruitment by two Mi2 homologues during C. elegans early embryonic development

The nucleosome remodeling and deacetylase complex promotes cell fate decisions throughout embryonic development. Its core enzymatic subunit, the SNF2-like ATPase and Helicase Mi2, is well conserved throughout ...

Authors: Stéphanie Käser-Pébernard, Catherine Pfefferli, Caroline Aschinger and Chantal Wicky

Erratum to: CBP binding outside of promoters and enhancers in Drosophila melanogaster

Authors: Philge Philip, Ann Boija, Roshan Vaid, Allison M. Churcher, David J. Meyers, Philip A. Cole, Mattias Mannervik and Per Stenberg

Pax6 associates with H3K4-specific histone methyltransferases Mll1, Mll2, and Set1a and regulates H3K4 methylation at promoters and enhancers

Pax6 is a key regulator of the entire cascade of ocular lens formation through specific binding to promoters and enhancers of batteries of target genes. The promoters and enhancers communicate with each other ...

Authors: Jian Sun, Yilin Zhao, Rebecca McGreal, Yamit Cohen-Tayar, Shira Rockowitz, Carola Wilczek, Ruth Ashery-Padan, David Shechter, Deyou Zheng and Ales Cvekl

The cnidarian Hydractinia echinata employs canonical and highly adapted histones to pack its DNA

Cnidarians are a group of early branching animals including corals, jellyfish and hydroids that are renowned for their high regenerative ability, growth plasticity and longevity. Because cnidarian genomes are ...

Authors: Anna Török, Philipp H. Schiffer, Christine E. Schnitzler, Kris Ford, James C. Mullikin, Andreas D. Baxevanis, Antony Bacic, Uri Frank and Sebastian G. Gornik

The cancer-associated CTCFL/BORIS protein targets multiple classes of genomic repeats, with a distinct binding and functional preference for humanoid-specific SVA transposable elements

A common aberration in cancer is the activation of germline-specific proteins. The DNA-binding proteins among them could generate novel chromatin states, not found in normal cells. The germline-specific transc...

Authors: Elena M. Pugacheva, Evgeny Teplyakov, Qiongfang Wu, Jingjing Li, Cheng Chen, Chengcheng Meng, Jian Liu, Susan Robinson, Dmitry Loukinov, Abdelhalim Boukaba, Andrew Paul Hutchins, Victor Lobanenkov and Alexander Strunnikov