Single cell analysis pushes the boundaries of TAD formation and function.

Abstract:

:Eukaryotic genomes encode genetic information in their linear sequence, but appropriate expression of their genes requires chromosomes to fold into complex three-dimensional structures. Fueled by a growing collection of sequencing and imaging-based technologies, studies have uncovered a hierarchy of DNA interactions, from small chromatin loops that connect genes and enhancers to larger topologically associated domains (TADs) and compartments. However, despite the remarkable conservation of these organizational features, we have a very limited understanding of how this organization influences gene expression. This issue is further complicated in the context of single-cell heterogeneity, as has recently been revealed at both the level of gene activation and chromatin topology. Here, we provide a perspective on recent studies that address cell-to-cell variability and the relationship between structural heterogeneity and gene expression. We propose that transcription is regulated by variable 3D structures driven by at least two independent and partially redundant mechanisms. Collectively, this may provide flexibility to transcriptional regulation at the level of individual cells as well as reproducibility across whole tissues.

journal_name

Curr Opin Genet Dev

authors

Luppino JM,Joyce EF

doi

10.1016/j.gde.2020.03.005

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

25-31

eissn

0959-437X

issn

1879-0380

pii

S0959-437X(20)30034-4

journal_volume

61

pub_type

杂志文章,评审
  • Turning germ cells into stem cells.

    abstract::Primordial germ cells (PGCs), the embryonic precursors of the gametes of the adult animal, can give rise to two types of pluripotent stem cells. In vivo, PGCs can give rise to embryonal carcinoma cells, the pluripotent stem cells of testicular tumors. Cultured PGCs exposed to a specific cocktail of growth factors give...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2003.08.010

    authors: Donovan PJ,de Miguel MP

    更新日期:2003-10-01 00:00:00

  • Vertebrate craniofacial development: novel approaches and new dilemmas.

    abstract::Unexpected patterns of neuroblast, angioblast and myoblast movement and tissue organization have been defined using lineage tracing and transplantation methods. The most novel and enigmatic new data derive from analyses of genes in the Hox- and Pax-gene families. In addition to the characterization of expression patte...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-437x(05)80175-3

    authors: Noden DM

    更新日期:1992-08-01 00:00:00

  • Establishment of cell type specific gene transcription during sporulation in Bacillus subtilis.

    abstract::Asymmetric cell division during the process of sporulation in the bacterium Bacillus subtilis generates dissimilar progeny that exhibit distinct programs of gene transcription. Recent work reveals a partner switching mechanism that governs the activity of the sporulation regulatory protein sigma F and that may be resp...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/0959-437x(94)90127-o

    authors: Duncan L,Alper S,Losick R

    更新日期:1994-10-01 00:00:00

  • Spatial aspects of intracellular information processing.

    abstract::The computational properties of intracellular biochemical networks, for which the cell is assumed to be a 'well-mixed' reactor, have already been widely characterized. What has so far not received systematic treatment is the important role of space in many intracellular computations. Spatial network computations can b...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2009.12.006

    authors: Kinkhabwala A,Bastiaens PI

    更新日期:2010-02-01 00:00:00

  • MCM proteins: DNA damage, mutagenesis and repair.

    abstract::The MCM2-7 complex, which may act as a replicative helicase during DNA synthesis, plays a central role in S-phase genome stability. MCM proteins are required for processive DNA replication and are a target of S-phase checkpoints. Loss of MCM function causes DNA damage and genome instability. MCM expression is upregula...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2003.11.002

    authors: Bailis JM,Forsburg SL

    更新日期:2004-02-01 00:00:00

  • Incapacitating the evolutionary capacitor: Hsp90 modulation of disease.

    abstract::The nature-nurture argument surrounding the mechanisms of disease causation cannot be resolved, as the roles of genes and environment are inextricably entwined. Environmental fluctuation is clearly a major modifier of phenotype, as well as a promoter of evolutionary change. Both types of variability can be mediated by...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2008.07.004

    authors: Yeyati PL,van Heyningen V

    更新日期:2008-06-01 00:00:00

  • Image analysis for understanding embryo development: a bridge from microscopy to biological insights.

    abstract::The digital reconstruction of the embryogenesis of model organisms from 3D+time data is revolutionizing practices in quantitative and integrative Developmental Biology. A manual and fully supervised image analysis of the massive complex data acquired with new microscopy technologies is no longer an option and automate...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2011.08.001

    authors: Luengo-Oroz MA,Ledesma-Carbayo MJ,Peyriéras N,Santos A

    更新日期:2011-10-01 00:00:00

  • Mapping the journey from totipotency to lineage specification in the mouse embryo.

    abstract::Understanding the past is to understand the present. Mammalian life, with all its complexity comes from a humble beginning of a single fertilized egg cell. Achieving this requires an enormous diversification of cellular function, the majority of which is generated through a series of cellular decisions during embryoge...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2015.08.002

    authors: Leung CY,Zernicka-Goetz M

    更新日期:2015-10-01 00:00:00

  • A quantitative approach to understanding vertebrate limb morphogenesis at the macroscopic tissue level.

    abstract::To understand organ morphogenetic mechanisms, it is essential to clarify how spatiotemporally-regulated molecular/cellular dynamics causes physical tissue deformation. In the case of vertebrate limb development, while some of the genes and oriented cell behaviors underlying morphogenesis have been revealed, tissue def...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2017.04.005

    authors: Suzuki T,Morishita Y

    更新日期:2017-08-01 00:00:00

  • To loop or not to loop: what is the role of TADs in enhancer function and gene regulation?

    abstract::The past decade has seen a huge jump in the resolution and scale at which we can interrogate the three-dimensional properties of the genome. This revealed different types of chromatin structures including topologically associating domains, partitioning genes and their enhancers into interacting domains. While the visu...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2020.12.015

    authors: Cavalheiro GR,Pollex T,Furlong EE

    更新日期:2021-01-23 00:00:00

  • Colonial ascidians as model organisms for the study of germ cells, fertility, whole body regeneration, vascular biology and aging.

    abstract::Colonial ascidians are marine invertebrate chordates that are the closest invertebrate relative to the vertebrates. Colonies of Botryllus schlosseri undergo a continuous asexual reproduction process that involves the regeneration of entire new bodies, which include all somatic and germline tissues. This adult regenera...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2016.06.001

    authors: Kassmer SH,Rodriguez D,De Tomaso AW

    更新日期:2016-08-01 00:00:00

  • microRNAs, the cell's Nepenthe: clearing the past during the maternal-to-zygotic transition and cellular reprogramming.

    abstract::The maternal-to-zygotic transition (MZT) is a universal step in animal development characterized by two major events: activation of zygotic transcription and degradation of maternally provided mRNAs. How zygotic gene products instruct the degradation of maternal messages remains a long-standing question in biology. Mi...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2010.04.003

    authors: Giraldez AJ

    更新日期:2010-08-01 00:00:00

  • Should evolutionary geneticists worry about higher-order epistasis?

    abstract::Natural selection drives evolving populations up the fitness landscape, the projection from nucleotide sequence space to organismal reproductive success. While it has long been appreciated that topographic complexities on fitness landscapes can arise only as a consequence of epistatic interactions between mutations, e...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2013.10.007

    authors: Weinreich DM,Lan Y,Wylie CS,Heckendorn RB

    更新日期:2013-12-01 00:00:00

  • The role of somatic mosaicism in brain disease.

    abstract::In this review we discuss the importance of genetic somatic mosaicism and its impact on brain diseases. We start from introducing the different types of somatic mutations, their frequencies and abundances across development and lifespan. We then describe how weakness in DNA repair mechanisms influences their prevalenc...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2020.05.002

    authors: Jourdon A,Fasching L,Scuderi S,Abyzov A,Vaccarino FM

    更新日期:2020-12-01 00:00:00

  • AngiomiRs--key regulators of angiogenesis.

    abstract::The formation of new blood vessels through the process of angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to a variety of diseases, such as ischemia and cancer. Recent studies have revealed important roles for miRNAs in regulating endothelial cell (EC) function, especially...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2009.04.002

    authors: Wang S,Olson EN

    更新日期:2009-06-01 00:00:00

  • Cornelia de Lange Syndrome and the link between chromosomal function, DNA repair and developmental gene regulation.

    abstract::Cornelia de Lange Syndrome (CdLS) is a rare multiple malformation disorder with characteristic facial features, growth and cognitive retardation, and many other abnormalities. CdLS individuals were recently shown to have heterozygous mutations in a previously uncharacterised gene, NIPBL, which encodes delangin, a homo...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2005.04.005

    authors: Strachan T

    更新日期:2005-06-01 00:00:00

  • Epigenetic regulation of mouse preimplantation embryo development.

    abstract::After fertilization, mouse embryos go through preimplantation development to give rise to blastocyst. Two key molecular events, zygotic genome activation (ZGA) and the first cell lineage specification, are essential for the process. Recent advances in low-input epigenomics profiling techniques allow the analysis of th...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2020.05.015

    authors: Fu X,Zhang C,Zhang Y

    更新日期:2020-10-01 00:00:00

  • Inter-chromosomal gene regulation in the mammalian cell nucleus.

    abstract::Cellular phenotypes can critically rely on mono-allelic gene expression. Recent studies suggest that in mammalian cells inter-chromosomal DNA interactions may mediate the decision which allele to activate and which to silence. Here, these findings are discussed in the context of knowledge on gene competition, chromati...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2007.07.009

    authors: de Laat W,Grosveld F

    更新日期:2007-10-01 00:00:00

  • miSSING LINKS: miRNAs and plant development.

    abstract::The discovery of hundreds of plant micro RNAs (miRNAs) has triggered much speculation about their potential roles in plant development. The search for plant genes involved in miRNA processing has revealed common factors such as DICER, and new molecules, including HEN1. Progress is also being made toward identifying mi...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-437x(03)00081-9

    authors: Hunter C,Poethig RS

    更新日期:2003-08-01 00:00:00

  • Molecular pathogenesis of peripheral neuropathies: insights from Drosophila models.

    abstract::Peripheral neuropathies are characterized by degeneration of peripheral motor, sensory and/or autonomic axons, leading to progressive distal muscle weakness, sensory deficits and/or autonomic dysfunction. Acquired peripheral neuropathies, e.g., as a side effect of chemotherapy, are distinguished from inherited periphe...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2017.01.011

    authors: Bussmann J,Storkebaum E

    更新日期:2017-06-01 00:00:00

  • Chromatin organization: form to function.

    abstract::Recent developments in technology have made it possible to create high resolution genome-wide maps of histone marks, DNA binding proteins and physical interactions along genomic regions. Chromatin features are found together in different combinations, dividing the genome up into domains with distinct functional proper...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2012.11.011

    authors: de Graaf CA,van Steensel B

    更新日期:2013-04-01 00:00:00

  • Synthetic transcription factors for cell fate reprogramming.

    abstract::The ability to reprogram cell lineage specification through the activity of master regulatory transcription factors has transformed disease modeling, drug screening, and cell therapy for regenerative medicine. Recent advances in the engineering of synthetic transcription factors to modulate endogenous gene expression ...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2018.05.001

    authors: Black JB,Gersbach CA

    更新日期:2018-10-01 00:00:00

  • Genetics of type 1 diabetes.

    abstract::Type 1 diabetes is the most common autoimmune disorder in childhood, characterized by the development of autoimmunity through unknown environmental insults in genetically susceptible individuals. There are now over 50 regions of the genome that harbor type 1 diabetes susceptibility genes, with much of the genetic risk...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2018.01.006

    authors: Robertson CC,Rich SS

    更新日期:2018-06-01 00:00:00

  • Myc-Max-Mad: a transcription factor network controlling cell cycle progression, differentiation and death.

    abstract::The Myc oncoprotein dimerizes with its partner, Max, to bind DNA, activate transcription, and promote cell proliferation, as well as programmed cell death. Max also forms homodimers or heterodimers with its alternative partners, Mad and Mxi-1. These complexes behave as antagonists of Myc/Max through competition for co...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/0959-437x(94)90098-1

    authors: Amati B,Land H

    更新日期:1994-02-01 00:00:00

  • Size isn't everything: lessons in genetic miniaturisation from nucleomorphs.

    abstract::Nucleomorphs are the vestigial nuclear genomes of eukaryotic algal cells now existing as endosymbionts within a host cell. Molecular investigation of the endosymbiont genomes has allowed important insights into the process of eukaryote/eukaryote cell endosymbiosis and has also disclosed a plethora of interesting genet...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-437x(97)80043-3

    authors: Gilson PR,Maier UG,McFadden GI

    更新日期:1997-12-01 00:00:00

  • Establishing myogenic identity during somitogenesis.

    abstract::Over the past year, interest has focused on identifying signalling molecules--including Wnts, Sonic hedgehog, BMP-4, and noggin--that divert somitic mesodermal cells into the muscle lineage, either by induction or derepression. New mouse mutants have also provided insights into somite formation and differentiation, as...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-437x(97)80011-1

    authors: Tajbakhsh S,Cossu G

    更新日期:1997-10-01 00:00:00

  • Cohesin and chromatin organisation.

    abstract::Cohesin defines the topology of chromosomes in mitosis and meiosis by holding sister chromatids together; more recently a role for cohesin in chromatin organisation and gene expression in interphase has emerged. ...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2011.11.003

    authors: Seitan VC,Merkenschlager M

    更新日期:2012-04-01 00:00:00

  • Comparative primate genomics: the year of the chimpanzee.

    abstract::This is the year of the chimpanzee genome. Chimpanzee chromosome 22 has been sequenced and soon will be followed by the whole genome, and thousands of chimpanzee cDNA sequences are available for comparative analysis. Not only does this genomic information allow us to identify human-specific changes in particular genes...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2004.08.007

    authors: Ruvolo M

    更新日期:2004-12-01 00:00:00

  • SINEs.

    abstract::SINEs with internal promoters for RNA polymerase III are ubiquitous in the genomes of the animal kingdom, including invertebrates. Although the human Alu family, and related families, originates from 7SL RNA, all other SINEs originate from tRNA. SINEs have been amplified many times, altered in genomic organization and...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/s0959-437x(05)80198-4

    authors: Okada N

    更新日期:1991-12-01 00:00:00

  • The mechanisms shaping the single-cell transcriptional landscape.

    abstract::Recent technological and computational advances in understanding the transcriptional and chromatin features of single cells have begun answering longstanding questions in the extent and impact of biological heterogeneity. Here, we outline the intrinsic and extrinsic mechanisms that underlie the transcriptional and fun...

    journal_title:Current opinion in genetics & development

    pub_type: 杂志文章,评审

    doi:10.1016/j.gde.2015.11.004

    authors: Martinez-Jimenez CP,Odom DT

    更新日期:2016-04-01 00:00:00