Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins

Ringrose, Leonie; Paro, Renato

doi:10.1146/annurev.genet.38.072902.091907

Cited by 975 publications

(875 citation statements)

References 129 publications

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“…The Polycomb group proteins (PcG) constitute a cellular memory system that maintains the heritable repression of genes (Ringrose and Paro, 2004;Martin and Zhang, 2005). The Polycomb targets include genes that function in cell proliferation, differentiation and tumorigenesis.…”

Section: Introduction Results and Discussionmentioning

confidence: 99%

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

et al. 2007

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BelgiumPSP94, for prostatic secretory protein of 94 amino acids, is secreted by the prostate gland and functions as a suppressor of tumor growth and metastasis. The expression of PSP94 is lost in advanced, hormone-refractory prostate cancer and this correlates with an increased expression of the Polycomb protein EZH2 (enhancer of zeste homolog 2), which represses transcription via trimethylation of histone H3 on Lys27 (H3K27). We show here that these events are causally related and that the MSMB gene, which encodes PSP94, is trimethylated on H3K27 in androgen-refractory, but not in androgensensitive prostate cancer cells. Chromatin immunoprecipitation experiments confirmed an association of EZH2 with the MSMB gene. The RNAi-mediated knockdown of EZH2 resulted in a loss of H3K27 trimethylation and an increased expression of the MSMB gene. Conversely, the overexpression of EZH2 was associated with a decreased expression of the MSMB gene. We also demonstrate that MSMB is additionally repressed in androgen-refractory prostate cancer cells by the hypoacetylation of histone H3K9 and the hypermethylation of a CpG island in the promoter region. Our data disclose a hitherto unexplored link between the putative oncogene EZH2 and the tumor suppressor PSP94, and show that MSMB is silenced by EZH2 in advanced prostate cancer cells.

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Section: Introduction Results and Discussionmentioning

confidence: 99%

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

et al. 2007

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“…Stable memory is biologically important for Hox genes to specify the identity of embryonic tissues (Ringrose and Paro, 2004), and epigenetic silencing can restrict the expression of Hox genes to specific cell types in the developing embryo. An important issue in studies of epigenetically mediated gene silencing is to understand whether DNA methylation is the initial silencing event or whether it is targeted to the region by earlier chromatin-remodeling events.…”

Section: Molecular Links Between Dna Methylation and Histone Modificamentioning

confidence: 99%

Epigenetic regulations in hematopoietic Hox code

Hua

Yan

2010

Oncogene

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“…Polycomb group (PcG) proteins and their associates, which mediate histone methylation, DNA methylation, and assembly of repressive proteins, are recruited to produce a stable, silenced state in the cell. For activation, Trithorax group (TrxG) proteins and associates mediate alternate modes of histone methylation, histone isoform replacement, and remodeling to produce an open chromatin state (Levine et al, 2004;Ringrose and Paro, 2004;Bantignies and Cavalli, 2006). These mechanisms remain unexplored in the retina and are little explored in the CNS.…”

Section: Thyroid Hormone Receptors Act As Sensors Of Thyroid Hormone T3mentioning

confidence: 99%

Transient expression of thyroid hormone nuclear receptor TRβ2 sets S opsin patterning during cone photoreceptor genesis

Applebury

Farhangfar

Glösmann

et al. 2007

Developmental Dynamics

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Cone photoreceptors in the murine retina are patterned by dorsal repression and ventral activation of S opsin. TR␤2, the nuclear thyroid hormone receptor ␤ isoform 2, regulates dorsal repression. To determine the molecular mechanism by which TR␤2 acts, we compared the spatiotemporal expression of TR␤2 and S opsin from embryonic day (E) 13 through adulthood in C57BL/6 retinae. TR␤2 and S opsin are expressed in cone photoreceptors only. Both are transcribed by E13, and their levels increase with cone genesis. TR␤2 is expressed uniformly, but transiently, across the retina. mRNA levels are maximal by E17 at completion of cone genesis and again minimal before P5. S opsin is also transcribed by E13, but only in ventral cones. Repression in dorsal cones is established by E17, consistent with the occurrence of patterning during cone cell genesis. The uniform expression of TR␤2 suggests that repression of S opsin requires other dorsalspecific factors in addition to TR␤2. The mechanism by which TR␤2 functions was probed in transgenic animals with TR␤2 ablated, TR␤2 that is DNA binding defective, and TR␤2 that is ligand binding defective. These studies show that TR␤2 is necessary for dorsal repression, but not ventral activation of S opsin. TR␤2 must bind DNA and the ligand T3 (thyroid hormone) to repress S opsin. Once repression is established, T3 no longer regulates dorsal S opsin repression in adult animals. The transient, embryonic action of TR␤2 is consistent with a role (direct and/or indirect) in chromatin remodeling that leads to permanent gene silencing in terminally differentiated, dorsal cone photoreceptors.

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Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins

Cited by 975 publications

References 129 publications

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

The gene encoding the prostatic tumor suppressor PSP94 is a target for repression by the Polycomb group protein EZH2

Epigenetic regulations in hematopoietic Hox code

Transient expression of thyroid hormone nuclear receptor TRβ2 sets S opsin patterning during cone photoreceptor genesis

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