Polycomb Group Protein Displacement and Gene Activation through MSK-Dependent H3K27me3S28 Phosphorylation

Gehani, Simmi S.; Agrawal-Singh, Shuchi; Dietrich, Nikolaj; Christophersen, Nicolaj S.; Helin, Kristian; Hansen, Klaus

doi:10.1016/j.molcel.2010.08.020

Cited by 171 publications

(184 citation statements)

References 55 publications

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“…EGF induction has also been shown to induce rapid histone phosphorylation, namely the "nucleosomal response" (55). The phosphorylation of H3S10 and H3S28 via mitogen-and stressactivated kinases results in PcG displacement at a subset of immediate early and stress response genes by impeding Pc chromodomain binding to H3K27me3 (54,56). However, in our study, we do not observe a global displacement of Cbx7 from chromatin upon EGF treatment (e.g., Fig.…”

Section: Discussioncontrasting

confidence: 53%

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Mitogen-activated Protein Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7

Balsbaugh

Chandler

et al. 2013

Journal of Biological Chemistry

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Section: Discussioncontrasting

confidence: 53%

“…Protein phosphorylation is well recognized as an important mechanism for the regulation of cellular signaling, and a growing body of literature suggests that phosphorylation regulates chromatin dynamics (24,45,54). Here, we report a novel phosphorylation site on mouse Cbx7 that is highly conserved.…”

Section: Discussionmentioning

confidence: 77%

Mitogen-activated Protein Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7

Balsbaugh

Chandler

et al. 2013

Journal of Biological Chemistry

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“…While this manuscript was under review, Gehani et al (30) reported similar findings in that H3 S28 phosphorylation, mediated by MSK1/2, was important for activation of polycomb target genes in response to mitogenic, stress, and differentiation signals. Their conclusions are completely consistent with our findings.…”

Section: Methodsmentioning

confidence: 63%

Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing

Lau

Cheung

2011

Proc. Natl. Acad. Sci. U.S.A.

157

166

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Histone H3 phosphorylation is a critical step that couples signal transduction pathways to gene regulation. To specifically assess the transcriptional regulatory functions of H3 phosphorylation, we developed an in vivo targeting approach and found that the H3 kinase MSK1 is a direct and potent transcriptional activator. Targeting of this H3 kinase to the endogenous c-fos promoter is sufficient to activate its expression without the need of upstream signaling. Moreover, targeting MSK1 to the α-globin promoter induces H3 S28 phosphorylation and reactivates expression of this polycomb-silenced gene. Importantly, we discovered a mechanism whereby H3 S28 phosphorylation not only displaces binding of the polycomb-repressive complexes, but it also induces a methylacetylation switch of the adjacent K27 residue. Our findings show that signal transduction activation can directly regulate polycomb silencing through a specific histone code-mediated mechanism.chromatin | gene expression | phospho-acetylation | methylation H 3 phosphorylation is a downstream event for a number of signal transduction pathways in mammalian cells (reviewed in refs. 1 and 2). For example, rapid and transient phosphorylation of H3 at S10 (H3S10ph) is detected at the promoters and coding regions of immediate-early (IE) genes upon stimulation of the MAPK or p38 pathways, suggesting that this signalinginduced histone modification functions to activate transcription of IE genes. Thus far, multiple kinases, including RSK2, MSK1/ 2, PIM1, and IKKα, have been shown to directly phosphorylate H3. As a common target of diverse signaling cascades, H3 phosphorylation is thought to be a critical step translating signal transduction information to the chromatin/transcriptional regulatory machinery (3).Currently, how H3 phosphorylation is mechanistically linked to the transcriptional process is still not fully understood. H3 S10 phosphorylation can be physically coupled to acetylation of nearby lysine residues (K9 or K14), suggesting that combinations of these modifications function together to activate transcription (4-6). Specific isoforms of 14-3-3 directly bind H3S10ph, and this interaction is greatly enhanced by additional acetylation of the nearby K14 residue, further illustrating the biological relevance of specific combinations of histone modifications (7,8). Finally, recruitment of 14-3-3 through H3S10ph at the promoters of HDAC1 and several IE genes is thought to facilitate transcription induction of these genes (7, 9, 10). Binding of 14-3-3 to H3S10ph at the FOSL1 enhancer, which is located downstream of the transcription start site, initiates sequential recruitment of the histone acetyltransferase (HAT) males absent on the first (MOF), the bromodomain-containing protein 4 (BRD4), and the positive transcription elongation factor b (P-TEFb) (10). At least for this particular gene, H3 S10 phosphorylation leads to the release of the preinitiated but paused RNA polymerase II (RNAP II) and facilitates transcriptional elongation. In addition to S10, H3 is a...

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“…One mechanism recently described is stress-induced reversal of polycomb repression by phosphorylation of serine 28 of histone H3 in mammals (14). Other candidates for this function are chromatin regulators that genetically act in opposition to polycomb repressors; these are collectively referred to as trithorax group (TrxG) proteins (8).…”

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confidence: 99%

SWI2/SNF2 chromatin remodeling ATPases overcome polycomb repression and control floral organ identity with the LEAFY and SEPALLATA3 transcription factors

Sang

Bezhani

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

198

194

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Patterning of the floral organs is exquisitely controlled and executed by four classes of homeotic regulators. Among these, the class B and class C floral homeotic regulators are of central importance as they specify the male and female reproductive organs. Inappropriate induction of the class B gene APETALA3 (AP3) and the class C gene AGAMOUS (AG) causes reduced reproductive fitness and is prevented by polycomb repression. At the onset of flower patterning, polycomb repression needs to be overcome to allow induction of AP3 and AG and formation of the reproductive organs. We show that the SWI2/SNF2 chromatin-remodeling ATPases SPLAYED (SYD) and BRAHMA (BRM) are redundantly required for flower patterning and for the activation of AP3 and AG. The SWI2/SNF2 ATPases are recruited to the regulatory regions of AP3 and AG during flower development and physically interact with two direct transcriptional activators of class B and class C gene expression, LEAFY (LFY) and SEPALLATA3 (SEP3). SYD and LFY association with the AP3 and AG regulatory loci peaks at the same time during flower patterning, and SYD binding to these loci is compromised in lfy and lfy sep3 mutants. This suggests a mechanism for SWI2/SNF2 ATPase recruitment to these loci at the right stage and in the correct cells. SYD and BRM act as trithorax proteins, and the requirement for SYD and BRM in flower patterning can be overcome by partial loss of polycomb activity in curly leaf (clf) mutants, implicating the SWI2/SNF2 chromatin remodelers in reversal of polycomb repression. P lant development occurs largely postembryonically (1), and, as a consequence, many cell-fate choices do not take place until long after embryogenesis. One example is flower development; in the rapid-flowering winter annual Arabidopsis the first flowers are formed 1 mo to 1 y after germination (2). Precocious activation of the floral homeotic genes required for flower patterning results in pleiotropic defects including poor seed set and is prevented by chromatin repression, which is faithfully inherited throughout cell divisions until the first flowers are formed (3-7). The repressive chromatin needs to be erased for flower patterning to be initiated in flower primordia. For class B genes, such as APETALA3 (AP3), which are required for correct patterning of the showy petals and the male reproductive organs, activation of gene expression occurs in late stage 2 flower primordia in the cells that will give rise to whorls 2 and 3 of the flower (6). For class C gene AGAMOUS (AG), which is required for patterning both the male and the female reproductive organs, induction is observed in early stage 3 flowers in the cells that will give rise to whorls 3 and 4 (6).The mitotically heritable chromatin repression of AP3 and AG before flower formation is achieved by two polycomb complexes: polycomb repressive complex 1 (PRC1) and PRC2. PRC2 is responsible for trimethylation of lysine 27 of histone H3 (H3K27me3) (7,8). Two putative H3K27 methyltransferases and PRC2 complex components, SWINGER and ...

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Polycomb Group Protein Displacement and Gene Activation through MSK-Dependent H3K27me3S28 Phosphorylation

Cited by 171 publications

References 55 publications

Mitogen-activated Protein Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7

Mitogen-activated Protein Kinase Signaling Mediates Phosphorylation of Polycomb Ortholog Cbx7

Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing

SWI2/SNF2 chromatin remodeling ATPases overcome polycomb repression and control floral organ identity with the LEAFY and SEPALLATA3 transcription factors

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