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  1. Artikel ; Online: SAF-A mutants disrupt chromatin structure through dominant negative effects on RNAs associated with chromatin.

    Kolpa, Heather J / Creamer, Kevin M / Hall, Lisa L / Lawrence, Jeanne B

    Mammalian genome : official journal of the International Mammalian Genome Society

    2021  Band 33, Heft 2, Seite(n) 366–381

    Abstract: Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear ...

    Abstract Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction. SAF-A has an N-terminal DNA binding domain and C-terminal RNA binding domain, and a prominent model has been that the protein provides a single-molecule bridge between XIST RNA and chromatin. Here analysis of the impact of SAF-A on broad RNA-chromatin interactions indicate greater biological complexity. We focus on SAF-A's role with repeat-rich C
    Mesh-Begriff(e) Chromatin/genetics ; Euchromatin ; Nuclear Proteins/genetics ; RNA, Long Noncoding/genetics ; X Chromosome
    Chemische Substanzen Chromatin ; Euchromatin ; Nuclear Proteins ; RNA, Long Noncoding
    Sprache Englisch
    Erscheinungsdatum 2021-12-02
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1058547-3
    ISSN 1432-1777 ; 0938-8990
    ISSN (online) 1432-1777
    ISSN 0938-8990
    DOI 10.1007/s00335-021-09935-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: SAF-A Requirement in Anchoring XIST RNA to Chromatin Varies in Transformed and Primary Cells.

    Kolpa, Heather J / Fackelmayer, Frank O / Lawrence, Jeanne B

    Developmental cell

    2016  Band 39, Heft 1, Seite(n) 9–10

    Mesh-Begriff(e) Chromatin ; Dosage Compensation, Genetic ; Humans ; RNA/genetics ; RNA, Long Noncoding ; RNA, Untranslated/genetics ; X Chromosome ; X Chromosome Inactivation
    Chemische Substanzen Chromatin ; RNA, Long Noncoding ; RNA, Untranslated ; RNA (63231-63-0)
    Sprache Englisch
    Erscheinungsdatum 2016-09-20
    Erscheinungsland United States
    Dokumenttyp Letter ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2054967-2
    ISSN 1878-1551 ; 1534-5807
    ISSN (online) 1878-1551
    ISSN 1534-5807
    DOI 10.1016/j.devcel.2016.09.021
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: Stable C0T-1 repeat RNA is abundant and is associated with euchromatic interphase chromosomes.

    Hall, Lisa L / Carone, Dawn M / Gomez, Alvin V / Kolpa, Heather J / Byron, Meg / Mehta, Nitish / Fackelmayer, Frank O / Lawrence, Jeanne B

    Cell

    2014  Band 156, Heft 5, Seite(n) 907–919

    Abstract: Recent studies recognize a vast diversity of noncoding RNAs with largely unknown functions, but few have examined interspersed repeat sequences, which constitute almost half our genome. RNA hybridization in situ using C0T-1 (highly repeated) DNA probes ... ...

    Abstract Recent studies recognize a vast diversity of noncoding RNAs with largely unknown functions, but few have examined interspersed repeat sequences, which constitute almost half our genome. RNA hybridization in situ using C0T-1 (highly repeated) DNA probes detects surprisingly abundant euchromatin-associated RNA comprised predominantly of repeat sequences (C0T-1 RNA), including LINE-1. C0T-1-hybridizing RNA strictly localizes to the interphase chromosome territory in cis and remains stably associated with the chromosome territory following prolonged transcriptional inhibition. The C0T-1 RNA territory resists mechanical disruption and fractionates with the nonchromatin scaffold but can be experimentally released. Loss of repeat-rich, stable nuclear RNAs from euchromatin corresponds to aberrant chromatin distribution and condensation. C0T-1 RNA has several properties similar to XIST chromosomal RNA but is excluded from chromatin condensed by XIST. These findings impact two "black boxes" of genome science: the poorly understood diversity of noncoding RNA and the unexplained abundance of repetitive elements.
    Mesh-Begriff(e) Animals ; Cell Nucleus/chemistry ; Chromosomes, Mammalian/chemistry ; Euchromatin/chemistry ; Humans ; Hybrid Cells ; Interphase ; Long Interspersed Nucleotide Elements ; Mice ; RNA, Untranslated/analysis ; RNA, Untranslated/genetics ; Repetitive Sequences, Nucleic Acid ; Transcription, Genetic
    Chemische Substanzen Euchromatin ; RNA, Untranslated
    Sprache Englisch
    Erscheinungsdatum 2014-03-01
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2014.01.042
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: miR-21 represses Pdcd4 during cardiac valvulogenesis.

    Kolpa, Heather J / Peal, David S / Lynch, Stacey N / Giokas, Andrea C / Ghatak, Shibnath / Misra, Suniti / Norris, Russell A / Macrae, Calum A / Markwald, Roger R / Ellinor, Patrick / Bischoff, Joyce / Milan, David J

    Development (Cambridge, England)

    2013  Band 140, Heft 10, Seite(n) 2172–2180

    Abstract: The discovery of small non-coding microRNAs has revealed novel mechanisms of post-translational regulation of gene expression, the implications of which are still incompletely understood. We focused on microRNA 21 (miR-21), which is expressed in cardiac ... ...

    Abstract The discovery of small non-coding microRNAs has revealed novel mechanisms of post-translational regulation of gene expression, the implications of which are still incompletely understood. We focused on microRNA 21 (miR-21), which is expressed in cardiac valve endothelium during development, in order to better understand its mechanistic role in cardiac valve development. Using a combination of in vivo gene knockdown in zebrafish and in vitro assays in human cells, we show that miR-21 is necessary for proper development of the atrioventricular valve (AV). We identify pdcd4b as a relevant in vivo target of miR-21 and show that protection of pdcd4b from miR-21 binding results in failure of AV development. In vitro experiments using human pulmonic valve endothelial cells demonstrate that miR-21 overexpression augments endothelial cell migration. PDCD4 knockdown alone was sufficient to enhance endothelial cell migration. These results demonstrate that miR-21 plays a necessary role in cardiac valvulogenesis, in large part due to an obligatory downregulation of PDCD4.
    Mesh-Begriff(e) Animals ; Apoptosis Regulatory Proteins/metabolism ; Cell Movement ; Crosses, Genetic ; Endothelial Cells/cytology ; Gene Expression Regulation, Developmental ; Heart Valves/embryology ; Humans ; Mice ; MicroRNAs/metabolism ; RNA-Binding Proteins/metabolism ; Time Factors ; Zebrafish ; Zebrafish Proteins/metabolism
    Chemische Substanzen Apoptosis Regulatory Proteins ; MIRN21 microRNA, human ; MIRN21 microRNA, mouse ; MIRN21 microRNA, zebrafish ; MicroRNAs ; PDCD4 protein, human ; Pdcd4 protein, mouse ; RNA-Binding Proteins ; Zebrafish Proteins ; pdcd4b protein, zebrafish
    Sprache Englisch
    Erscheinungsdatum 2013-04-11
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 90607-4
    ISSN 1477-9129 ; 0950-1991
    ISSN (online) 1477-9129
    ISSN 0950-1991
    DOI 10.1242/dev.084475
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Translating dosage compensation to trisomy 21.

    Jiang, Jun / Jing, Yuanchun / Cost, Gregory J / Chiang, Jen-Chieh / Kolpa, Heather J / Cotton, Allison M / Carone, Dawn M / Carone, Benjamin R / Shivak, David A / Guschin, Dmitry Y / Pearl, Jocelynn R / Rebar, Edward J / Byron, Meg / Gregory, Philip D / Brown, Carolyn J / Urnov, Fyodor D / Hall, Lisa L / Lawrence, Jeanne B

    Nature

    2013  Band 500, Heft 7462, Seite(n) 296–300

    Abstract: Down's syndrome is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21. We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST (the X- ... ...

    Abstract Down's syndrome is a common disorder with enormous medical and social costs, caused by trisomy for chromosome 21. We tested the concept that gene imbalance across an extra chromosome can be de facto corrected by manipulating a single gene, XIST (the X-inactivation gene). Using genome editing with zinc finger nucleases, we inserted a large, inducible XIST transgene into the DYRK1A locus on chromosome 21, in Down's syndrome pluripotent stem cells. The XIST non-coding RNA coats chromosome 21 and triggers stable heterochromatin modifications, chromosome-wide transcriptional silencing and DNA methylation to form a 'chromosome 21 Barr body'. This provides a model to study human chromosome inactivation and creates a system to investigate genomic expression changes and cellular pathologies of trisomy 21, free from genetic and epigenetic noise. Notably, deficits in proliferation and neural rosette formation are rapidly reversed upon silencing one chromosome 21. Successful trisomy silencing in vitro also surmounts the major first step towards potential development of 'chromosome therapy'.
    Mesh-Begriff(e) Animals ; Cell Line ; Cell Proliferation ; Chromosomes, Human, Pair 21/genetics ; DNA Methylation ; Dosage Compensation, Genetic ; Down Syndrome/genetics ; Down Syndrome/therapy ; Gene Silencing ; Humans ; Induced Pluripotent Stem Cells ; Male ; Mice ; Mutagenesis, Insertional ; Neurogenesis ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Sex Chromatin/genetics ; X Chromosome Inactivation/genetics
    Chemische Substanzen RNA, Long Noncoding ; XIST non-coding RNA
    Sprache Englisch
    Erscheinungsdatum 2013-07-17
    Erscheinungsland England
    Dokumenttyp 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/nature12394
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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