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  1. Article ; Online: LiMCA: Hi-C gets an RNA twist.

    Kawaoka, Jane / Lomvardas, Stavros

    Nature methods

    2024  

    Language English
    Publishing date 2024-04-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2169522-2
    ISSN 1548-7105 ; 1548-7091
    ISSN (online) 1548-7105
    ISSN 1548-7091
    DOI 10.1038/s41592-024-02205-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Olfactory receptor choice: a case study for gene regulation in a multi-enhancer system.

    Pourmorady, Ariel / Lomvardas, Stavros

    Current opinion in genetics & development

    2021  Volume 72, Page(s) 101–109

    Abstract: The mammalian genome possesses >2000 olfactory receptor (OR) alleles regulated by 63 known OR-Enhancer elements, yet each olfactory sensory neuron (OSN) expresses only a single OR allele. Choreographed changes to OSN nuclear architecture are evidently ... ...

    Abstract The mammalian genome possesses >2000 olfactory receptor (OR) alleles regulated by 63 known OR-Enhancer elements, yet each olfactory sensory neuron (OSN) expresses only a single OR allele. Choreographed changes to OSN nuclear architecture are evidently necessary for OR expression. Additionally, the insulated organization of OR-enhancers around an OR allele is a hallmark of the chosen OR. However, the biology guiding OR choice itself is unclear. Innovations in single-cell and biophysics-based analysis of nuclear architecture are revising previous models of the nucleus to include its dynamic and probabilistic nature. In this review, we ground current knowledge of OR gene regulation in these emerging theories to speculate on mechanisms that may give rise to diverse and singular OR expression.
    MeSH term(s) Animals ; Cell Nucleus/metabolism ; Gene Expression Regulation/genetics ; Mammals/genetics ; Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics ; Receptors, Odorant/metabolism ; Regulatory Sequences, Nucleic Acid
    Chemical Substances Receptors, Odorant
    Language English
    Publishing date 2021-12-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2021.11.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Editorial: Neural epigenetics.

    Greenberg, Michael E / Lomvardas, Stavros

    Current opinion in neurobiology

    2019  Volume 59, Page(s) iii–v

    Language English
    Publishing date 2019-11-27
    Publishing country England
    Document type Editorial
    ZDB-ID 1078046-4
    ISSN 1873-6882 ; 0959-4388
    ISSN (online) 1873-6882
    ISSN 0959-4388
    DOI 10.1016/j.conb.2019.11.001
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  4. Article ; Online: Olfactory receptor genes make the case for inter-chromosomal interactions.

    Bashkirova, Elizaveta / Lomvardas, Stavros

    Current opinion in genetics & development

    2019  Volume 55, Page(s) 106–113

    Abstract: The partitioning of the interphase nucleus into chromosome territories generally precludes DNA from making specific and reproducible inter-chromosomal contacts. However, with the development of powerful genomic and imaging tools for the analysis of the ... ...

    Abstract The partitioning of the interphase nucleus into chromosome territories generally precludes DNA from making specific and reproducible inter-chromosomal contacts. However, with the development of powerful genomic and imaging tools for the analysis of the 3D genome, and with their application on an increasing number of cell types, it becomes apparent that regulated, specific, and functionally important inter-chromosomal contacts exist. Widespread and stereotypic inter-chromosomal interactions are at the center of chemosensation, where they regulate the singular and stochastic expression of olfactory receptor genes. In olfactory sensory neurons (OSNs) coalescence of multiple intergenic enhancers to a multi-chromosomal hub orchestrates the expression of a single OR allele, whereas convergence of the remaining OR genes from 18 chromosomes into a few heterochromatic compartments mediates their effective transcriptional silencing. In this review we describe the role of interchromosomal interactions in OR gene choice, and we describe other biological systems where such genomic interactions may contribute to regulatory robustness and transcriptional diversification.
    MeSH term(s) Animals ; Cell Nucleus/genetics ; Cell Nucleus/metabolism ; Chromosomes/genetics ; Chromosomes/metabolism ; Gene Expression Regulation ; Humans ; Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics ; Receptors, Odorant/metabolism ; Regulatory Sequences, Nucleic Acid
    Chemical Substances Receptors, Odorant
    Language English
    Publishing date 2019-09-03
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1077312-5
    ISSN 1879-0380 ; 0959-437X
    ISSN (online) 1879-0380
    ISSN 0959-437X
    DOI 10.1016/j.gde.2019.07.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: LHX2- and LDB1-mediated trans interactions regulate olfactory receptor choice.

    Monahan, Kevin / Horta, Adan / Lomvardas, Stavros

    Nature

    2019  Volume 565, Issue 7740, Page(s) 448–453

    Abstract: The genome is partitioned into topologically associated domains and genomic compartments with shared chromatin valence. This architecture is constrained by the DNA polymer, which precludes interactions between genes on different chromosomes. Here we ... ...

    Abstract The genome is partitioned into topologically associated domains and genomic compartments with shared chromatin valence. This architecture is constrained by the DNA polymer, which precludes interactions between genes on different chromosomes. Here we report a marked divergence from this pattern of nuclear organization that occurs in mouse olfactory sensory neurons. Chromatin conformation capture using in situ Hi-C on fluorescence-activated cell-sorted olfactory sensory neurons and their progenitors shows that olfactory receptor gene clusters from 18 chromosomes make specific and robust interchromosomal contacts that increase with differentiation of the cells. These contacts are orchestrated by intergenic olfactory receptor enhancers, the 'Greek islands', which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression.
    MeSH term(s) Animals ; Cell Differentiation/genetics ; Chromatin/genetics ; Chromatin/metabolism ; Chromosome Positioning/genetics ; Chromosomes, Mammalian/genetics ; Chromosomes, Mammalian/metabolism ; DNA-Binding Proteins/metabolism ; Enhancer Elements, Genetic/genetics ; Female ; Gene Expression Regulation ; LIM Domain Proteins/metabolism ; LIM-Homeodomain Proteins/metabolism ; Male ; Mice ; Multigene Family/genetics ; Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics ; Receptors, Odorant/metabolism ; Transcription Factors/metabolism ; Transcription, Genetic
    Chemical Substances Chromatin ; DNA-Binding Proteins ; LIM Domain Proteins ; LIM-Homeodomain Proteins ; Ldb1 protein, mouse ; Lhx2 protein, mouse ; Receptors, Odorant ; Transcription Factors
    Language English
    Publishing date 2019-01-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-018-0845-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Book: Molecular mechanisms of olfactory receptor choice

    Lomvardas, Stavros

    (Neuroscience seminar series)

    2013  

    Abstract: CIT): Neuroscience Seminar Series Dr. Lomvardas Lab's research program aims to understand ...

    Institution National Institutes of Health (U.S.),
    Author's details Stavros Lomvardas
    Series title Neuroscience seminar series
    Abstract (CIT): Neuroscience Seminar Series Dr. Lomvardas Lab's research program aims to understand the molecular mechanisms of olfactory receptor gene choice. Olfactory receptor (OR) genes compose the largest mammalian gene family consisted of more than 1000 members. These genes are expressed in a stochastic and mutually exclusive fashion in such a way that only one OR allele is expressed in each olfactory sensory neuron. Their data suggest that this unusual expression pattern is orchestrated by a combination of positive and negative regulatory mechanism. According to their findings, OR genes undergo chromatin mediated silencing at a developmental stage that precedes olfactory receptor activation. One of the 3000 alleles is chosen for activation, by the enzymatic removal of the silencing chromatin marks. They currently combine genetic and biochemical approaches that together with cutting edge microscopy should reveal critical mechanistic details of this process.
    MeSH term(s) Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics
    Language English
    Size 1 online resource (1 streaming video file (1 hr., 3 min.) :, color, sound).
    Document type Book
    Note Title from title screen.
    Database Catalogue of the US National Library of Medicine (NLM)

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  7. Article ; Online: Histone and DNA Modifications as Regulators of Neuronal Development and Function.

    Lomvardas, Stavros / Maniatis, Tom

    Cold Spring Harbor perspectives in biology

    2016  Volume 8, Issue 7

    Abstract: DNA and histone modifications, together with constraints imposed by nuclear architecture, contribute to the transcriptional regulatory landscape of the nervous system. Here, we provide select examples showing how these regulatory layers, often referred ... ...

    Abstract DNA and histone modifications, together with constraints imposed by nuclear architecture, contribute to the transcriptional regulatory landscape of the nervous system. Here, we provide select examples showing how these regulatory layers, often referred to as epigenetic, contribute to neuronal differentiation and function. We describe the interplay between DNA methylation and Polycomb-mediated repression during neuronal differentiation, the role of DNA methylation and long-range enhancer-promoter interactions in Protocadherin promoter choice, and the contribution of heterochromatic silencing and nuclear organization in singular olfactory receptor expression. Finally, we explain how the activity-dependent expression of a histone variant determines the longevity of olfactory sensory neurons.
    MeSH term(s) DNA/chemistry ; DNA/physiology ; DNA Methylation ; Epigenesis, Genetic ; Histones/chemistry ; Histones/physiology ; Neurons/cytology ; Promoter Regions, Genetic
    Chemical Substances Histones ; DNA (9007-49-2)
    Language English
    Publishing date 2016-07-01
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 1943-0264
    ISSN (online) 1943-0264
    DOI 10.1101/cshperspect.a024208
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: RNA-mediated symmetry breaking enables singular olfactory receptor choice.

    Pourmorady, Ariel D / Bashkirova, Elizaveta V / Chiariello, Andrea M / Belagzhal, Houda / Kodra, Albana / Duffié, Rachel / Kahiapo, Jerome / Monahan, Kevin / Pulupa, Joan / Schieren, Ira / Osterhoudt, Alexa / Dekker, Job / Nicodemi, Mario / Lomvardas, Stavros

    Nature

    2023  Volume 625, Issue 7993, Page(s) 181–188

    Abstract: Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, where every olfactory neuron stably transcribes one of approximately 2,000 or more OR ... ...

    Abstract Olfactory receptor (OR) choice provides an extreme example of allelic competition for transcriptional dominance, where every olfactory neuron stably transcribes one of approximately 2,000 or more OR alleles
    MeSH term(s) Alleles ; Cell Lineage ; Enhancer Elements, Genetic/genetics ; Gene Expression Regulation ; Olfactory Receptor Neurons/metabolism ; Receptors, Odorant/genetics ; Receptors, Odorant/metabolism ; Regulatory Sequences, Nucleic Acid/genetics ; RNA/genetics ; Transcription, Genetic ; Genomics ; Single-Cell Analysis
    Chemical Substances Receptors, Odorant ; RNA (63231-63-0)
    Language English
    Publishing date 2023-12-20
    Publishing country England
    Document type Journal Article
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-023-06845-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Chemosensory receptor specificity and regulation.

    Dalton, Ryan P / Lomvardas, Stavros

    Annual review of neuroscience

    2015  Volume 38, Page(s) 331–349

    Abstract: The senses provide a means by which data on the physical and chemical properties of the environment may be collected and meaningfully interpreted. Sensation begins at the periphery, where a multitude of different sensory cell types are activated by ... ...

    Abstract The senses provide a means by which data on the physical and chemical properties of the environment may be collected and meaningfully interpreted. Sensation begins at the periphery, where a multitude of different sensory cell types are activated by environmental stimuli as different as photons and odorant molecules. Stimulus sensitivity is due to expression of different cell surface sensory receptors, and therefore the receptive field of each sense is defined by the aggregate of expressed receptors in each sensory tissue. Here, we review current understanding on patterns of expression and modes of regulation of sensory receptors.
    MeSH term(s) Animals ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/physiology ; Receptors, Odorant/genetics ; Receptors, Odorant/physiology ; Sensory Receptor Cells/physiology ; Vomeronasal Organ/physiology
    Chemical Substances Receptors, G-Protein-Coupled ; Receptors, Odorant ; taste receptors, type 1 ; taste receptors, type 2
    Language English
    Publishing date 2015-07-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 282459-0
    ISSN 1545-4126 ; 0147-006X
    ISSN (online) 1545-4126
    ISSN 0147-006X
    DOI 10.1146/annurev-neuro-071714-034145
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Monoallelic expression of olfactory receptors.

    Monahan, Kevin / Lomvardas, Stavros

    Annual review of cell and developmental biology

    2015  Volume 31, Page(s) 721–740

    Abstract: The sense of smell collects vital information about the environment by detecting a multitude of chemical odorants. Breadth and sensitivity are provided by a huge number of chemosensory receptor proteins, including more than 1,400 olfactory receptors (ORs) ...

    Abstract The sense of smell collects vital information about the environment by detecting a multitude of chemical odorants. Breadth and sensitivity are provided by a huge number of chemosensory receptor proteins, including more than 1,400 olfactory receptors (ORs). Organizing the sensory information generated by these receptors so that it can be processed and evaluated by the central nervous system is a major challenge. This challenge is overcome by monogenic and monoallelic expression of OR genes. The single OR expressed by each olfactory sensory neuron determines the neuron's odor sensitivity and the axonal connections it will make to downstream neurons in the olfactory bulb. The expression of a single OR per neuron is accomplished by coupling a slow chromatin-mediated activation process to a fast negative-feedback signal that prevents activation of additional ORs. Singular OR activation is likely orchestrated by a network of interchromosomal enhancer interactions and large-scale changes in nuclear architecture.
    MeSH term(s) Animals ; Axons/physiology ; Humans ; Odorants ; Olfactory Receptor Neurons/physiology ; Smell/physiology
    Language English
    Publishing date 2015
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1293750-2
    ISSN 1530-8995 ; 1081-0706
    ISSN (online) 1530-8995
    ISSN 1081-0706
    DOI 10.1146/annurev-cellbio-100814-125308
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