Differential Cooperation between Heterochromatin Protein HP1 Isoforms and MyoD in Myoblasts

Yahi, Hakima; Fritsch, Lauriane; Philipot, Ophélie; Guasconi, Valentina; Souidi, Mouloud; Robin, Philippe; Polesskaya, Anna; Losson, Régine; Harel‐Bellan, Annick; Ait‐Si‐Ali, Slimane

doi:10.1074/jbc.m802647200

Cited by 31 publications

(34 citation statements)

References 49 publications

(64 reference statements)

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“…Error bars calculated as the standard deviation between replicates. (*) P # 0.05, (**) P # 0.01. be recruited to specific promoters to silence transcription (Feldman et al 2006;Yahi et al 2008). In contrast, CBX3 was found to be more widely associated with euchromatin and is recruited to silence promoters by a variety of factors (Ogawa et al 2002;Vicent et al 2006;du Chene et al 2007;Liu et al 2010).…”

Section: Discussionmentioning

confidence: 99%

CBX3 regulates efficient RNA processing genome-wide

Smallwood¹,

Hon²,

Jin³

et al. 2012

Genome Res.

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CBX5, CBX1, and CBX3 (HP1α, β, and γ, respectively) play an evolutionarily conserved role in the formation and maintenance of heterochromatin. In addition, CBX5, CBX1, and CBX3 may also participate in transcriptional regulation of genes. Recently, CBX3 binding to the bodies of a subset of genes has been observed in human and murine cells. However, the generality of this phenomenon and the role CBX3 may play in this context are unknown. Genome-wide localization analysis reveals CBX3 binding at genic regions, which strongly correlates with gene activity across multiple cell types. Depletion of CBX3 resulted in down-regulation of a subset of target genes. Loss of CBX3 binding leads to a more dramatic accumulation of unspliced nascent transcripts. In addition, we observed defective recruitment of splicing factors, including SNRNP70, to CBX3 target genes. Collectively, our data suggest a role for CBX3 in aiding in efficient cotranscriptional RNA processing.

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Section: Discussionmentioning

confidence: 99%

CBX3 regulates efficient RNA processing genome-wide

Smallwood¹,

Hon²,

Jin³

et al. 2012

Genome Res.

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“…The role of HP1 family members during differentiation including skeletal muscle has had limited investigation [12], [13], [14], [15], [16], [17]. Recent reports, based primarily on heterologous systems, suggest that HP1 proteins might negatively regulate skeletal muscle differentiation by inhibiting skeletal muscle-specific factors, MEF2 and MyoD in myoblasts [12], [16].…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Regulation of Myogenic Gene Expression by Heterochromatin Protein 1 Alpha

et al. 2013

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Heterochromatin protein 1 (HP1) is an essential heterochromatin-associated protein typically involved in the epigenetic regulation of gene silencing. However, recent reports have demonstrated that HP1 can also activate gene expression in certain contexts including differentiation. To explore the role of each of the three mammalian HP1 family members (α, β and γ) in skeletal muscle, their expression was individually disrupted in differentiating skeletal myocytes. Among the three isoforms of HP1, HP1α was specifically required for myogenic gene expression in myoblasts only. Knockdown of HP1α led to a defect in transcription of skeletal muscle-specific genes including Lbx1, MyoD and myogenin. HP1α binds to the genomic region of myogenic genes and depletion of HP1α results in a paradoxical increase in histone H3 lysine 9 trimethylation (H3K9me3) at these sites. JHDM3A, a H3K9 demethylase also binds to myogenic gene’s genomic regions in myoblasts in a HP1α-dependent manner. JHDM3A interacts with HP1α and knockdown of JHDM3A in myoblasts recapitulates the decreased myogenic gene transcription seen with HP1α depletion. These results propose a novel mechanism for HP1α-dependent gene activation by interacting with the demethylase JHDM3A and that HP1α is required for maintenance of myogenic gene expression in myoblasts.

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“…Immunoblotting was performed with either anti-KAP1 antibody (ab10483, Abcam) followed by HRP-conjugated anti-rabbit antibody or HRP-conjugated anti-HA antibody (12013819001, Roche). Ex vivo GST pull-down assay was performed as previously described (Yahi et al 2008). …”

Section: Coimmunoprecipitation and Gst Pull-downmentioning

confidence: 99%

Evolutionally dynamic L1 regulation in embryonic stem cells

et al. 2014

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Mobile elements are important evolutionary forces that challenge genomic integrity. Long interspersed element-1 (L1, also known as LINE-1) is the only autonomous transposon still active in the human genome. It displays an unusual pattern of evolution, with, at any given time, a single active L1 lineage amplifying to thousands of copies before getting replaced by a new lineage, likely under pressure of host restriction factors, which act notably by silencing L1 expression during early embryogenesis. Here, we demonstrate that in human embryonic stem (hES) cells, KAP1 (KRAB [Krü ppel-associated box domain]-associated protein 1), the master cofactor of KRAB-containing zinc finger proteins (KRAB-ZFPs) previously implicated in the restriction of endogenous retroviruses, represses a discrete subset of L1 lineages predicted to have entered the ancestral genome between 26.8 million and 7.6 million years ago. In mice, we documented a similar chronologically conditioned pattern, albeit with a much contracted time scale. We could further identify an L1-binding KRAB-ZFP, suggesting that this rapidly evolving protein family is more globally responsible for L1 recognition. KAP1 knockdown in hES cells induced the expression of KAP1-bound L1 elements, but their younger, human-specific counterparts (L1Hs) were unaffected. Instead, they were stimulated by depleting DNA methyltransferases, consistent with recent evidence demonstrating that the PIWI-piRNA (PIWI-interacting RNA) pathway regulates L1Hs in hES cells. Altogether, these data indicate that the early embryonic control of L1 is an evolutionarily dynamic process and support a model in which newly emerged lineages are first suppressed by DNA methylation-inducing small RNA-based mechanisms before KAP1-recruiting protein repressors are selected.

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Differential Cooperation between Heterochromatin Protein HP1 Isoforms and MyoD in Myoblasts

Cited by 31 publications

References 49 publications

CBX3 regulates efficient RNA processing genome-wide

CBX3 regulates efficient RNA processing genome-wide

Epigenetic Regulation of Myogenic Gene Expression by Heterochromatin Protein 1 Alpha

Evolutionally dynamic L1 regulation in embryonic stem cells

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