HP1 and the dynamics of heterochromatin maintenance

Maison, Christèle; Almouzni, Geneviève

doi:10.1038/nrm1355

Cited by 546 publications

(527 citation statements)

References 95 publications

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“…In our experimental model, cells with silenced BRG1 showed increased resistance to nuclease digestion when compared with controls ( Figure 4a). The g-isoform of heterochromatic protein 1 (HP1-g) is a heterochromatic adaptor molecule involved in higher-order chromatin structure (Maison and Almouzni, 2004). It is widely used to identify heterochromatic foci in cell nuclei.…”

Section: Senescence Is Associated With Changes In Chromatin Statusmentioning

confidence: 99%

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

et al. 2010

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We focused our attention on brahma-related gene 1 (BRG1), the ATPase subunit of the SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex, and analyzed its role in mesenchymal stem cell (MSC) biology. We hypothesized that deviation from the correct concentration of these proteins, which act at the highest level of gene regulation, may be deleterious for cells. We wanted to know what would happen if a cell had to cope with altered regulation of gene expression, either by upregulation or downregulation of BRG1. We assumed that cells would try to restore homeostasis or, alternatively, that the event could trigger senescence/apoptosis phenomena. To this end, in MSCs, we silenced BRG1gene. Knockdown of BRG1 expression induced a significant increase in senescent cells and decrease in apoptotic cells. It is interesting that BRG1 downregulation also induced an increase in heterochromatin. At the molecular level, these phenomena were associated with activation of retinoblastoma-like protein 2 (RB2)/P130-and P53-related pathways. Senescence was accompanied by reduced expression of some stemness-related genes. This is consistent with our previous research, which showed that BRG1 upregulation by ectopic expression also induced senescence processes. Together, these data suggest that BRG1 belongs to a class of genes whose expression is tightly regulated; hence, subtle alterations in BRG1 activity seem to negatively affect mechanisms regulating chromatin status and, in turn, impair cellular physiology.

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Section: Senescence Is Associated With Changes In Chromatin Statusmentioning

confidence: 99%

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

et al. 2010

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“…4,5 The heterochromatin protein 1 (HP1) family, which comprises three closely related paralogs in mammals (HP1α, β and γ), 6 represents a prominent group of non-histone proteins with essential roles in heterochromatin formation/ maintenance and heterochromatin-related gene silencing. 7 A current model for HP1 function in pericentric heterochromatin involves SUMOylation of HP1 and non-coding RNA for its targeting. 8 Maintenance pathways exploit the interaction of HP1 N-terminal chromodomain (CD) with histone H3 tri-methylated on Lysine 9 (H3K9me3), a modification that is highly enriched in heterochromatin, 7 as well as its capacity to homoand hetero-dimerize via its C-terminal chromoshadow domain (CSD).…”

Section: Introductionmentioning

confidence: 99%

“…7 A current model for HP1 function in pericentric heterochromatin involves SUMOylation of HP1 and non-coding RNA for its targeting. 8 Maintenance pathways exploit the interaction of HP1 N-terminal chromodomain (CD) with histone H3 tri-methylated on Lysine 9 (H3K9me3), a modification that is highly enriched in heterochromatin, 7 as well as its capacity to homoand hetero-dimerize via its C-terminal chromoshadow domain (CSD). In addition, several HP1 partners 9,10 bind to the interface between two CSDs, which promote the activity of HP1 paralogs in various nuclear processes, such as transcriptional activation heterochromatin protein 1 paralogs (hp1α, β and γ in mammals) are not only central in heterochromatin organization, but have also been linked to transcriptional activation at euchromatic regions, maintenance of telomere stability and, most recently, to the DNa damage response (DDR).…”

Section: Introductionmentioning

confidence: 99%

Differential contribution of HP1 proteins to DNA end resection and homology-directed repair

Soria

Almouzni

2013

Cell Cycle

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“…[25][26][27] HP1a plays an important role in transcriptional repression of pericentromeric heterochromatin, where it directly interacts with H3K9me3 through its chromodomain. [28][29][30][31][32] Although both KDM2A-LF and KDM2A-SF are known to directly interact with HP1a, only KDM2A-LF has been studied with regards to regulation of pericentromeric heterochromatin. 33 Moreover, KDM2A-SF has been found to be overexpressed in cancer cells and to promote their proliferation most likely through its ability to induce rDNA transcription.…”

Section: Introductionmentioning

confidence: 99%

A demethylation deficient isoform of the lysine demethylase KDM2A interacts with pericentromeric heterochromatin in an HP1a-dependent manner

Lađinović

Novotná

Jakšová

et al. 2017

Nucleus

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Histone modifications have a profound impact on the chromatin structure and gene expression and their correct establishment and recognition is essential for correct cell functioning. Malfunction of histone modifying proteins is associated with developmental defects and diseases and detailed characterization of these proteins is therefore very important. The lysine specific demethylase KDM2A is a CpG island binding protein that has been studied predominantly for its ability to regulate CpG island-associated gene promoters by demethylating their H3K36me2. However, very little attention has been paid to the alternative KDM2A isoform that lacks the N-terminal demethylation domain, KDM2A-SF. Here we characterized KDM2A-SF more in detail and we found that, unlike the canonical full length KDM2A-LF isoform, KDM2A-SF forms distinct nuclear heterochromatic bodies in an HP1a dependent manner. Our chromatin immunoprecipitation experiments further showed that KDM2A binds to transcriptionally silent pericentromeric regions that exhibit high levels of H3K36me2. H3K36me2 is the substrate of the KDM2A demethylation activity and the high levels of this histone modification in the KDM2A-bound pericentromeric regions imply that these regions are occupied by the demethylation deficient KDM2A-SF isoform.

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HP1 and the dynamics of heterochromatin maintenance

Cited by 546 publications

References 95 publications

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

The BRG1 ATPase of chromatin remodeling complexes is involved in modulation of mesenchymal stem cell senescence through RB–P53 pathways

Differential contribution of HP1 proteins to DNA end resection and homology-directed repair

A demethylation deficient isoform of the lysine demethylase KDM2A interacts with pericentromeric heterochromatin in an HP1a-dependent manner

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