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  1. Article ; Online: Linker histone H1 regulates homeostasis of heterochromatin-associated cRNAs.

    Bujosa, Paula / Reina, Oscar / Caballé, Adrià / Casas-Lamesa, Anna / Torras-Llort, Mònica / Pérez-Roldán, Juan / Nacht, Ana Silvina / Vicent, Guillermo P / Bernués, Jordi / Azorín, Fernando

    Cell reports

    2024  Volume 43, Issue 5, Page(s) 114137

    Abstract: Chromatin-associated RNAs (cRNAs) are a poorly characterized fraction of cellular RNAs that co-purify with chromatin. Their full complexity and the mechanisms regulating their packaging and chromatin association remain poorly understood. Here, we address ...

    Abstract Chromatin-associated RNAs (cRNAs) are a poorly characterized fraction of cellular RNAs that co-purify with chromatin. Their full complexity and the mechanisms regulating their packaging and chromatin association remain poorly understood. Here, we address these questions in Drosophila. We find that cRNAs constitute a heterogeneous group of RNA species that is abundant in heterochromatic transcripts. We show that heterochromatic cRNAs interact with the heterogeneous nuclear ribonucleoproteins (hnRNP) hrp36/hrp48 and that depletion of linker histone dH1 impairs this interaction. dH1 depletion induces the accumulation of RNA::DNA hybrids (R-loops) in heterochromatin and, as a consequence, increases retention of heterochromatic cRNAs. These effects correlate with increased RNA polymerase II (RNAPII) occupancy at heterochromatin. Notably, impairing cRNA assembly by depletion of hrp36/hrp48 mimics heterochromatic R-loop accumulation induced by dH1 depletion. We also show that dH1 depletion alters nucleosome organization, increasing accessibility of heterochromatin. Altogether, these perturbations facilitate annealing of cRNAs to the DNA template, enhancing R-loop formation and cRNA retention at heterochromatin.
    Language English
    Publishing date 2024-04-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.114137
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Linker histone H1 prevents R-loop accumulation and genome instability in heterochromatin.

    Bayona-Feliu, Aleix / Casas-Lamesa, Anna / Reina, Oscar / Bernués, Jordi / Azorín, Fernando

    Nature communications

    2017  Volume 8, Issue 1, Page(s) 283

    Abstract: Linker histone H1 is an important structural component of chromatin that stabilizes the nucleosome and compacts the nucleofilament into higher-order structures. The biology of histone H1 remains, however, poorly understood. Here we show that Drosophila ... ...

    Abstract Linker histone H1 is an important structural component of chromatin that stabilizes the nucleosome and compacts the nucleofilament into higher-order structures. The biology of histone H1 remains, however, poorly understood. Here we show that Drosophila histone H1 (dH1) prevents genome instability as indicated by the increased γH2Av (H2AvS137P) content and the high incidence of DNA breaks and sister-chromatid exchanges observed in dH1-depleted cells. Increased γH2Av occurs preferentially at heterochromatic elements, which are upregulated upon dH1 depletion, and is due to the abnormal accumulation of DNA:RNA hybrids (R-loops). R-loops accumulation is readily detectable in G1-phase, whereas γH2Av increases mainly during DNA replication. These defects induce JNK-mediated apoptosis and are specific of dH1 depletion since they are not observed when heterochromatin silencing is relieved by HP1a depletion. Altogether, our results suggest that histone H1 prevents R-loops-induced DNA damage in heterochromatin and unveil its essential contribution to maintenance of genome stability.While structural importance of linker histone H1 in packaging eukaryotic genome into chromatin is well known, its biological function remains poorly understood. Here the authors reveal that Drosophila linker histone H1 prevents DNA:RNA hybrids accumulation and genome instability in heterochromatin.
    MeSH term(s) Animals ; Animals, Genetically Modified ; Cell Line ; Chromatin/genetics ; Chromatin/metabolism ; DNA Damage ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism ; Drosophila melanogaster/cytology ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Gene Expression Profiling/methods ; Genomic Instability ; Heterochromatin/genetics ; Heterochromatin/metabolism ; Histones/genetics ; Histones/metabolism ; RNA Interference
    Chemical Substances Chromatin ; Drosophila Proteins ; Heterochromatin ; Histones
    Language English
    Publishing date 2017-08-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-017-00338-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Histone H1: Lessons from Drosophila.

    Bayona-Feliu, Aleix / Casas-Lamesa, Anna / Carbonell, Albert / Climent-Cantó, Paula / Tatarski, Milos / Pérez-Montero, Salvador / Azorín, Fernando / Bernués, Jordi

    Biochimica et biophysica acta

    2016  Volume 1859, Issue 3, Page(s) 526–532

    Abstract: Eukaryotic genomes are structured in the form of chromatin with the help of a set of five small basic proteins, the histones. Four of them are highly conserved through evolution, form the basic unit of the chromatin, the nucleosome, and have been ... ...

    Abstract Eukaryotic genomes are structured in the form of chromatin with the help of a set of five small basic proteins, the histones. Four of them are highly conserved through evolution, form the basic unit of the chromatin, the nucleosome, and have been intensively studied and are well characterized. The fifth histone, histone H1, adds to this basic structure through its interaction at the entry/exit site of DNA in the nucleosome and makes an essential contribution to the higher order folding of the chromatin fiber. Histone H1 is the less conserved histone and the less known of them. Though for long time considered as a general repressor of gene expression, recent studies in Drosophila have rejected this view and have contributed to uncover important functions on genome stability and development. Here we present some of the most recent data obtained in the Drosophila model system and discuss how the lessons learnt in these studies compare and could be applied to all other eukaryotes.
    MeSH term(s) Amino Acid Sequence ; Animals ; Drosophila ; Genomic Instability ; Heterochromatin/chemistry ; Histones/chemistry ; Histones/physiology ; Molecular Sequence Data
    Chemical Substances Heterochromatin ; Histones
    Language English
    Publishing date 2016-03
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbagrm.2015.09.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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