Gene regulation articles within Nature Communications

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  • Article
    | Open Access

    De novo DNA methylation is carried out by DNMT3A and DNMT3B, but the distinct functions of these two enzymes is poorly understood. Here the authors present a comprehensive, genome-wide identification of target sites for de novo DNA methylation by the DNMT3A and DNMT3B in mouse ES cells and embryos, identifying unique de novo DNA methylation target sites for both DNMT3 enzymes.

    • Masaki Yagi
    • , Mio Kabata
    •  & Yasuhiro Yamada

  • Article
    | Open Access

    Genetic variation associated with gene expression changes has mostly been studied in the context of single nucleotide variants. Here, Jakubosky et al. report eQTL analysis of structural variants and short tandem repeats and find properties, such as length of variation, that affect the association.

    • David Jakubosky
    • , Matteo D’Antonio
    •  & Kelly A. Frazer

  • Article
    | Open Access

    Immune cells are important regulators of adipose tissue function, including adaptive thermogenesis. Here the authors show that mice with Krüppel-like factor 3 (KLF3) deficiency in bone marrow-derived cells have increased adipose tissue beiging which may at least in part be due to altered eosinophil paracrine signaling.

    • Alexander J. Knights
    • , Emily J. Vohralik
    •  & Kate G. R. Quinlan

  • Article
    | Open Access

    The unfolded protein response (UPR) is a stress response pathway implicated in numerous diseases and chemotherapy resistance. Here, the authors define the UPR regulon with a multi-omics strategy, uncovering changes to mitochondrial one-carbon metabolism and concomitant resistance to folate-based therapeutics.

    • Stefan Reich
    • , Chi D. L. Nguyen
    •  & Jan Medenbach

  • Article
    | Open Access

    The relationship between regulatory elements, chromatin interactions and gene expression during development remains poorly understood. Here the authors present Tiled-C, a low-input 3C approach to study genome architecture at high resolution, and apply it to mouse erythroid differentiation in vivo, finding that enhancer-promoter interactions are formed gradually during differentiation, concomitant with progressive upregulation of gene activity.

    • A. Marieke Oudelaar
    • , Robert A. Beagrie
    •  & Jim R. Hughes

  • Article
    | Open Access

    Local activity of the DNA methylation machinery remains poorly understood. Here, the authors present a theoretical and experimental framework to infer methylation and demethylation rates at genome scale in mouse embryonic stem cells, finding that maintenance methylation activity is reduced at transcription factor binding sites, while methylation turnover is elevated in transcribed gene bodies.

    • Paul Adrian Ginno
    • , Dimos Gaidatzis
    •  & Dirk Schübeler

  • Article
    | Open Access

    While DNA methylation is thought to play a regulatory role, there are few examples where modification of a single CpG dinucleotide directly affects transcription factor binding. Here the authors show that methylation of a single CGATA element within the c-Kit gene inhibits binding and regulation by erythroid transcription factor GATA-1, both in cells and in mice, suggesting that methylation at this site plays an essential role in erythropoiesis.

    • Lu Yang
    • , Zhiliang Chen
    •  & Merlin Crossley

  • Article
    | Open Access

    Characterization of the distance over which TF binding influences gene expression is important for inferring target genes. Here the authors study this relationship using thousands of genomic data sets, finding two classes of TFs with distinct ranges of regulatory influence modulated by chromatin states of topologically associated domains.

    • Chen-Hao Chen
    • , Rongbin Zheng
    •  & X. Shirley Liu

  • Article
    | Open Access

    Dysregulation of mRNA alternative splicing is prevalent in cancers. Here, the authors characterized the landscape of aberrant alternative splicing during the development of prostate cancer, progression and therapeutic resistance and show that splicing modulator, E7107, reduces growth in castration-resistant prostate cancer.

    • Dingxiao Zhang
    • , Qiang Hu
    •  & Dean G. Tang

  • Article
    | Open Access

    Synthetic genetic circuits are sensitive to their environment and host cell, requiring many rounds of physical reassembly to achieve a desired function. Here the authors use a multi-level regulatory motif to dynamically tune the function of genetic parts as a step towards robust adaptive circuits.

    • Vittorio Bartoli
    • , Grace A. Meaker
    •  & Thomas E. Gorochowski

  • Article
    | Open Access

    Long noncoding RNAs (lncRNAs) regulate key steps of cell division. Here, the authors perform a comprehensive RNAi imaging screen targeting more than 2,000 human lncRNAs, and suggest a role of chromatin-associated linc00899 in regulation of cell division by suppressing the transcription of microtubule-binding protein TPPP/p25.

    • Lovorka Stojic
    • , Aaron T. L. Lun
    •  & Fanni Gergely

  • Article
    | Open Access

    A fraction of mammalian CTCF binding sites fall within transposable elements (TEs) but their contribution to the evolution of 3D chromatin structure is unknown. Here the authors investigate the effect of TE-driven CTCF binding site expansions on chromatin looping in humans and mice, and provide evidence that TEs contribute to cell-specific and species-specific chromatin looping diversity and variable gene regulation in mammalian genomes.

    • Adam G. Diehl
    • , Ningxin Ouyang
    •  & Alan P. Boyle

  • Article
    | Open Access

    The ability to grow at acidic pH is crucial for E. coli colonization of the host’s intestine. Here, the authors identify an acid-tolerance response system that is important for E. coli exponential growth at pH 4.2, survival in the mouse intestine, and production of 3-hydroxypropionate during fermentation.

    • Ying Xu
    • , Zhe Zhao
    •  & Guang Zhao

  • Article
    | Open Access

    The transcription factor PfAP2-G is a key determinant of sexual commitment in Plasmodium falciparum. Here, Josling et al. define the transcriptional regulatory network of PfAP2-G by identifying its DNA binding sites genome-wide, which vary depending on the route of sexual conversion and rely on interactions with the PfAP2-I transcription factor.

    • Gabrielle A. Josling
    • , Timothy J. Russell
    •  & Manuel Llinás

  • Article
    | Open Access

    Identification of silencer elements by computational or experimental approaches in a genome-wide manner is still challenging. Here authors define uncharacterized cis-regulatory elements (CREs) in human and mouse genomes likely containing silencer elements, and test them in cells using massively parallel reporter assays to identify silencer elements that showed silencer activity.

    • Naresh Doni Jayavelu
    • , Ajay Jajodia
    •  & R. David Hawkins

  • Article
    | Open Access

    Somatic mutations in MED12 have been implicated as the causal genetic lesion in the majority of uterine leiomyomas. Here, the authors profile the chromatin landscape of matched normal and leiomyoma tissues and find that changes in enhancer acetylation, enhancer-promoter interaction strength, differential enhancer usage and transcription factor AP-1 occupancy are significant drivers of transcriptional dysregulation in MED12 mutant leiomyomas.

    • Mthabisi B. Moyo
    • , J. Brandon Parker
    •  & Debabrata Chakravarti

  • Article
    | Open Access

    Small non-coding RNAs contribute to the regulation of aging. Here the authors identify a small nucleolar RNA, the snoRNA jouvence, which extends the lifespan of fruit flies through its function in the gut, and is conserved in humans.

    • Stéphanie Soulé
    • , Lucille Mellottée
    •  & Jean-René Martin

  • Article
    | Open Access

    Metabolic adaptation to different diets results in changes to gene expression. Here, the authors characterise the chromatin landscape and transcriptional network in mice on a diet of high saturated fat, compared to a diet high in carbohydrate, finding a dramatic reprogramming of the liver transcriptional network.

    • Yufeng Qin
    • , Sara A. Grimm
    •  & Paul A. Wade

  • Article
    | Open Access

    In Drosophila, transcription is thought to be required for TAD formation, while the role of architectural proteins remains controversial. Here, the authors find that deletion of domain boundaries at the fly Notch locus results in TAD fusion and long-range topological defects, loss of architectural protein and RNA Pol II chromatin binding, and transcription defects.

    • Rodrigo G. Arzate-Mejía
    • , Angel Josué Cerecedo-Castillo
    •  & Félix Recillas-Targa

  • Article
    | Open Access

    Antibody production in plasma cells involves the unfold protein response (UPR), but how this is regulated is not clear. Here the authors show that mTORC1 signalling but not Xbp1-mediated transcription regulation in activated B cells is important for the induction of a UPR-related transcriptome that precedes full plasma cell functions.

    • Brian T. Gaudette
    • , Derek D. Jones
    •  & David Allman

  • Article
    | Open Access

    PU.1 is a master TF of hematopoietic lineage differentiation. Here the authors analyse properties of PU.1 DNA-binding in vitro and genome-wide in vivo across different cell types with native or ectopic PU.1 expression, and uncover the mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1.

    • Julia Minderjahn
    • , Andreas Schmidt
    •  & Michael Rehli

  • Article
    | Open Access

    For most human genes nearby regulatory variants explain only a small proportion of their expression variation between individuals. Here the authors show how the impact of a gene’s set of nearby regulatory variant is often linked to the expression levels of distal genes, providing insights into gene networks.

    • D. Wragg
    • , Q. Liu
    •  & J. G. D. Prendergast

  • Article
    | Open Access

    The understanding of the changes regulating gene expression relevant for the emergence of the human brain and its susceptibility to disease is limited. Here, the authors identified a set of regulatory elements that evolved in hominins affecting oligodendrocyte function, and link these to autism.

    • Bas Castelijns
    • , Mirna L. Baak
    •  & Menno P. Creyghton

  • Article
    | Open Access

    The functional significance of start site choice in promoter architectures is little understood. Here the authors identify in zebrafish development and mammalian cells a class of dual-initiation promoters, in which non-canonical YC dinucleotides reflecting 5’-TOP/TCT initiation are intertwined with canonical YR-initiation.

    • Chirag Nepal
    • , Yavor Hadzhiev
    •  & Ferenc Müller

  • Article
    | Open Access

    Although transcription factor (TF) cooperativity is widespread, a global mechanistic understanding of the role of TF cooperativity is still lacking. Here the authors introduce a statistical learning framework that provides structural insight into TF cooperativity and its functional consequences based on next generation sequencing data and provide mechanistic insights into TF cooperativity and its impact on protein-phenotype interactions.

    • Ignacio L. Ibarra
    • , Nele M. Hollmann
    •  & Judith B. Zaugg

  • Article
    | Open Access

    In C. elegans the chaperone hsp-16.2 predicts the penetrance of mutations and lifespan after heat shock, but it is not known why cells express different amounts of hsp-16.2. Here the authors show hsp-16.2 tracks differences in global gene expression capacity, rather than differences in signaling or intrinsic noise in adult intestine cells.

    • Nikolay Burnaevskiy
    • , Bryan Sands
    •  & Alexander Mendenhall

  • Article
    | Open Access

    Although most are silenced, certain transposable elements (TEs) have been co-opted by the host. Here, the authors quantify the epigenomic status of TEs using data from the Roadmap Epigenomics Project, provide a systematic profile of TE activity across normal human tissues and development, finding that TEs encompass a quarter of the human regulatory epigenome, with 47% of TEs in regulatory states.

    • Erica C. Pehrsson
    • , Mayank N. K. Choudhary
    •  & Ting Wang

  • Article
    | Open Access

    The coordination of interactions between multiple regulatory elements and genes within a chromatin domain remains poorly understood. Here, the authors use a method to detect multi-way chromatin interactions in a mouse model in which the α-globin domain is extended to include several additional genes, finding that the promoters do not form mutually exclusive interactions with the enhancers, but all interact simultaneously in a single complex.

    • A. Marieke Oudelaar
    • , Caroline L. Harrold
    •  & Jim R. Hughes

  • Article
    | Open Access

    In Drosophila, dosage compensation involves a twofold transcriptional upregulation of the single male chromosome X. Here the authors show that global conformational differences are specifically present in the male X chromosome and detectable using Hi-C data, indicating that dosage compensation affects global chromosome structure.

    • Koustav Pal
    • , Mattia Forcato
    •  & Francesco Ferrari

  • Article
    | Open Access

    Proper ovarian differentiation requires RUNX1. Here, the authors show that double knockout of Runx1/Foxl2 results in masculinization of fetal ovaries, and that RUNX1 and FOXL2 jointly occupy common chromatin regions to maintain pre-granulosa cell identity in the fetal ovary.

    • Barbara Nicol
    • , Sara A. Grimm
    •  & Humphrey H.-C. Yao

  • Article
    | Open Access

    Mutations associated with SCN5A, which encodes the major cardiac sodium channel, influence impulse conduction and are associated with arrhythmia disorders. Here, the authors identify an evolutionary conserved, super enhancer-like, regulatory cluster downstream of SCN5A and show that it controls the chromatin architecture of the locus and Scn5a expression.

    • Joyce C. K. Man
    • , Rajiv A. Mohan
    •  & Vincent M. Christoffels

  • Article
    | Open Access

    In multiple myeloma, a 4;14 translocation induces overexpression of histone methyltransferase NSD2, resulting in expansion of H3K36me2 and shrinkage of H3K27me3 domains. Here the authors find that CTCF, H3K27ac and gene expression changes cluster within a subset of insulated domains implicating 3D chromosome organization as a key factor in the NSD2-mediated phenotype.

    • Priscillia Lhoumaud
    • , Sana Badri
    •  & Jane A. Skok

  • Article
    | Open Access

    Trophectoderm lineage development is essential for implantation, placentation, and healthy pregnancy. Here the authors map super-enhancers (SEs) in trophoblast stem cells and find both TE-specific master regulators and 150 previous uncharacterised transcription factors that are SE-associated, providing insight into trophectoderm-specific regulatory networks.

    • Bum-Kyu Lee
    • , Yu jin Jang
    •  & Jonghwan Kim

  • Article
    | Open Access

    The majority of disease-associated genetic variants lie in non-coding regions. Here the authors generated and compiled human transcriptomic, epigenomic and chromatin conformation datasets, to identify genes associated with atrial fibrillation and functional non-coding variants.

    • Antoinette F. van Ouwerkerk
    • , Fernanda M. Bosada
    •  & Vincent M. Christoffels

  • Article
    | Open Access

    Gene dosage anomalies such as those caused by aneuploidy underlie diseases including Down syndrome. Here, the authors perform allele-specific single cell transcriptome analysis to investigate the mechanisms of gene dosage imbalance in fibroblasts with trisomies T21, T18, T13 and T8.

    • Georgios Stamoulis
    • , Marco Garieri
    •  & Stylianos E. Antonarakis

  • Article
    | Open Access

    In plants, 3′ Pol II pausing helps prevent transcriptional interference. Here the authors provide evidence that BORDER proteins are enriched in intergenic regions and inhibit transcriptional interference between closely spaced genes by preventing RNA polymerase from intruding into the promoters of nearby downstream genes.

    • Xuhong Yu
    • , Pascal G. P. Martin
    •  & Scott D. Michaels

  • Article
    | Open Access

    Tet-mediated DNA demethylation is intimately involved in reguatling embryonic development. Here the authors characterise DNA methylation and hydroxymethylation dynamics during early cardiac development in both human and mice and provide evidence that Tet-mediated DNA demethylation plays a role in regulating chromatin organization during early heart development.

    • Shaohai Fang
    • , Jia Li
    •  & Yun Huang

  • Article
    | Open Access

    In yeast, Hda1 histone deacetylase complex (Hda1C) preferentially deacetylates H3 and H2B, but has also been implicated in global H4 deacetylation. Here, the authors provide evidence that Hda1C binds to hyperactive genes, where it specifically deacetylates H4 to partially inhibit elongation, suggesting a role for Hda1C in elongation by specifically deacetylating H4 at highly transcribed regions.

    • So Dam Ha
    • , Seokjin Ham
    •  & TaeSoo Kim

  • Article
    | Open Access

    The role of CTCF-bound insulator elements in enhancer-gene interactions and transcriptional regulation remains poorly understood. Here, the authors investigate multiple epigenome editing strategies for perturbing individual CTCF-bound insulators, and evaluate their effects on genome topology and transcription.

    • Daniel R. Tarjan
    • , William A. Flavahan
    •  & Bradley E. Bernstein

  • Article
    | Open Access

    UPF1 mediates the decay of target mRNA in a 3′ untranslated region (UTR)-length-dependent manner. Here the authors reveal that the 3′UTR-length-dependent regulation of UPF1-dependent mRNA decay occurs through EJC-independent but miRNA-dependent regulation.

    • Jungyun Park
    • , Jwa-Won Seo
    •  & Jin-Wu Nam

  • Article
    | Open Access

    In prostate cancer, chromatin structure can impact the transcriptome. Here, the authors develop high resolution chromatin interaction maps in prostate cancer cells using in situ Hi-C, revealing prostate cancer-specific TADs and enhancer-promoter loops surrounding the androgen receptor (AR) locus.

    • Suhn Kyong Rhie
    • , Andrew A. Perez
    •  & Peggy J. Farnham

  • Article
    | Open Access

    Polycomb Repressive Complex 2 (PRC2) plays critical roles in transcriptional silencing during development. Here the authors identify EZHIP as a cofactor of PRC2 expressed predominantly in the gonads, finding that EZHIP limits the enzymatic activity of PRC2 in germ cells in mice.

    • Roberta Ragazzini
    • , Raquel Pérez-Palacios
    •  & Raphaël Margueron

  • Article
    | Open Access

    Pioneer transcription factor Pax7 specifies melanotrope cells, which then allows for the binding of Tpit transcription factor. Here, authors find that while binding of heterochromatin targeting by Pax7 is independent of Tpit, Pax7-dependent chromatin opening requires Tpit.

    • Alexandre Mayran
    • , Kevin Sochodolsky
    •  & Jacques Drouin

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