Neutralization of the Positive Charges on Histone Tails by RNA Promotes an Open Chromatin Structure

Dueva, Rositsa; Akopyan, Karen; Pederiva, Chiara; Trevisan, Davide M.; Dhanjal, Soniya; Lindqvist, Arne; Farnebo, Marianne

doi:10.1016/j.chembiol.2019.08.002

Cited by 65 publications

(38 citation statements)

References 50 publications

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“…Although these lncRNA-mediated regulatory mechanisms should be explored individually, RNA has inherent regulatory potential. The negative charge of RNA can neutralize the positively charged www.nature.com/nrm histone tails, leading to chromatin de-compaction 38 , so RNA-mediated opening and closing of chromatin might function as a rapid switch of gene expression. Mechanistically, both cis-acting and trans-acting nuclear lncRNAs establish interactions with DNA to alter the chromatin environment, sometimes indirectly by virtue of their affinity for proteins that can associate with both RNA and DNA, and in other cases by binding DNA in a sequence-specific manner.…”

Section: Chromatin Regulationmentioning

confidence: 99%

Gene regulation by long non-coding RNAs and its biological functions

Statello

Guo

Chen

et al. 2020

Nat Rev Mol Cell Biol

3,178

2,317

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Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA and proteins, lncRNAs can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic mRNAs and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that lncRNAs are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.

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Section: Chromatin Regulationmentioning

confidence: 99%

Gene regulation by long non-coding RNAs and its biological functions

Statello

Guo

Chen

et al. 2020

Nat Rev Mol Cell Biol

3,178

2,317

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“…These data indicate that the N-ter RNA-binding domain of H2A.L.2 could be an important element in controlling the nuclear localization of the protein. In our test model of NIH3T3 cells, nonspecific RNA-binding by H2A.L.2 could decrease the tropism of H2A.L.2 for the transcriptionally silent RNA-poor heterochromatin regions, probably by mediating the stabilization of H2A.L.2 on other genomic regions via chromatin-bound RNAs [21].…”

Section: Pericentric Localization Of H2al2 Is Controlled By Its N-tmentioning

confidence: 85%

RNA-Guided Genomic Localization of H2A.L.2 Histone Variant

Hoghoughi

Barral

Curtet

et al. 2020

Cells

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The molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B-H2A.L.2 allows a controlled replacement of histones by protamines to occur. Here, we highlight the intrinsic ability of H2A.L.2 to specifically target the pericentric regions of the genome and discuss why pericentric heterochromatin is a privileged site of histone retention in mature spermatozoa. We observed that the intranuclear localization of H2A.L.2 is controlled by its ability to bind RNA, as well as by an interplay between its RNA-binding activity and its tropism for pericentric heterochromatin. We identify the H2A.L.2 RNA-binding domain and demonstrate that in somatic cells, the replacement of H2A.L.2 RNA-binding motif enhances and stabilizes its pericentric localization, while the forced expression of RNA increases its homogenous nuclear distribution. Based on these data, we propose that the specific accumulation of RNA on pericentric regions combined with H2A.L.2 tropism for these regions are responsible for stabilizing H2A.L.2 on these regions in mature spermatozoa. This situation would favor histone retention on pericentric heterochromatin.

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“…RNA appears to be a functional component of chromatin (Brockdorff, 2019; Michieletto and Gilbert, 2019; Rodriguez-Campos and Azorin, 2007), but its molecular contribution is not well understood. One recent study proposes that chromatin-associated RNA promotes open chromatin structures by neutralising the positive charges on histone tails (Dueva et al, 2019). SAF-A could assist this process by tethering RNA molecules in the proximity of chromatin.…”

Section: Discussionmentioning

confidence: 99%

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

Connolly

Takahashi

Miura

et al. 2021

Preprint

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The organisation of chromatin is closely intertwined with biological activities of chromosome domains, including transcription and DNA replication status. Scaffold attachment factor A (SAF-A), also known as Heteronuclear Ribonucleoprotein Protein U (HNRNPU), contributes to the formation of open chromatin structure. Here we demonstrate that SAF-A promotes the normal progression of DNA replication, and enables resumption of replication after inhibition. We report that cells depleted for SAF-A show reduced origin licensing in G1 phase, and consequently reduced origin activation frequency in S phase. Replication forks progress slowly in cells depleted for SAF-A, also contributing to reduced DNA synthesis rate. Single-cell replication timing analysis revealed that the boundaries between early- and late- replicating domains are blurred in cells depleted for SAF-A. Associated with these defects, SAF-A-depleted cells show elevated gH2A phosphorylation and tend to enter quiescence. Overall we find that SAF-A protein promotes robust DNA replication to ensure continuing cell proliferation.

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Neutralization of the Positive Charges on Histone Tails by RNA Promotes an Open Chromatin Structure

Cited by 65 publications

References 50 publications

Gene regulation by long non-coding RNAs and its biological functions

Gene regulation by long non-coding RNAs and its biological functions

RNA-Guided Genomic Localization of H2A.L.2 Histone Variant

SAF-A promotes origin licensing and replication fork progression to ensure robust DNA replication

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