Trans-silencing by P Elements Inserted in Subtelomeric Heterochromatin Involves the Drosophila Polycomb Group Gene, Enhancer of Zeste

AbstractDrosophila P-element transposition is regulated by a maternally inherited state known as P cytotype. An important aspect of P cytotype is transcriptional repression of the P-element promoter. P cytotype can also repress non-P-element promoters within P-element ends, suggesting that P cytotype repression might involve chromatin-based transcriptional silencing. To learn more about the role of chromatin in P cytotype repression, we have been studying the P strain Lk-P(1A). This strain contains two full-length P elements inserted in the heterochromatic telomere-associated sequences (TAS elements) at cytological location 1A. Mutations in the Polycomb group gene (Pc-G gene), Enhancer of zeste (E(z)), whose protein product binds at 1A, resulted in a loss of Lk-P(1A) cytotype control. E(z) mutations also affected the trans-silencing of heterologous promoters between P-element termini by P-element transgenes inserted in the TAS repeats. These data suggest that pairing interactions between P elements, resulting in exchange of chromatin structures, may be a mechanism for controlling the expression and activity of P elements.

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Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate gene silencing in Drosophila heterochromatin and at S.cerevisiae telomeres

The EMBO Journal ◽

10.1093/emboj/16.11.3219 ◽

1997 ◽

Vol 16 (11) ◽

pp. 3219-3232 ◽

Cited By ~ 184

Author(s):

G. Laible

Keyword(s):

Gene Silencing ◽

Polycomb Group ◽

Enhancer Of Zeste ◽

Gene Enhancer ◽

Drosophila Heterochromatin ◽

Polycomb Group Gene

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The Drosophila Polycomb-group gene Enhancer of zeste contains a region with sequence similarity to trithorax

Molecular and Cellular Biology ◽

10.1128/mcb.13.10.6357-6366.1993 ◽

1993 ◽

Vol 13 (10) ◽

pp. 6357-6366

Author(s):

R S Jones ◽

W M Gelbart

Keyword(s):

Amino Acids ◽

Sequence Similarity ◽

Protein Product ◽

Polycomb Group ◽

Acute Leukemias ◽

Trithorax Group ◽

Acid Protein ◽

Enhancer Of Zeste ◽

Gene Enhancer ◽

Carboxy Terminal

As is typical of Polycomb-group loci, the Enhancer of zeste [E(z)] gene negatively regulates the segment identity genes of the Antennapedia (ANT-C) and Bithorax (BX-C) gene complexes. A second class of loci, collectively known as the trithorax group, plays an antagonistic role as positive regulators of the ANT-C and BX-C genes. Molecular analysis of the E(z) gene predicts a 760-amino-acid protein product. A region of 116 amino acids near the E(z) carboxy terminus is 41.2% identical (68.4% similar) with a carboxy-terminal region of the trithorax protein. This portion of the trithorax protein is part of a larger region previously shown to share extensive homology with a human protein (ALL-1/Hrx) that is implicated in acute leukemias. Over this same 116 amino acids, E(z) and ALL-1/Hrx are 43.9% identical (68.4% similar). Otherwise, E(z) is not significantly similar to any previously described proteins. As this region of sequence similarity is shared by two proteins with antagonistic functions, we suggest that it may comprise a domain that interacts with a common target, either nucleic acid or protein. Opposite effects on transcription might then be determined by other portions of the two proteins.

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E(z): a polycomb group gene or a trithorax group gene?

Development ◽

10.1242/dev.122.7.2189 ◽

1996 ◽

Vol 122 (7) ◽

pp. 2189-2197 ◽

Cited By ~ 6

Author(s):

D. LaJeunesse ◽

A. Shearn

Keyword(s):

Polycomb Group ◽

Bithorax Complex ◽

Trithorax Group ◽

Polycomb Group Genes ◽

Enhancer Of Zeste ◽

Selector Genes ◽

Homeotic Selector Genes ◽

Polycomb Group Gene ◽

Anterior Posterior ◽

Homeotic Selector

The products of the Polycomb group of genes are cooperatively involved in repressing expression of homeotic selector genes outside of their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of Polycomb group genes results in the ectopic expression of both Antennapedia Complex and Bithorax Complex genes. The products of the trithorax group of genes are cooperatively involved in maintaining active expression of homeotic selector genes within their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of trithorax group genes results in reduced expression of both Antennapedia Complex and Bithorax Complex genes. Although Enhancer of zeste has been classified as a member of the Polycomb group, in this paper we show that Enhancer of zeste can also be classified as a member of the trithorax group. The requirement for Enhancer of zeste activity as either a trithorax group or Polycomb group gene depends on the homeotic selector gene locus as well as on spatial and temporal cues.

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The Drosophila Polycomb-group gene Enhancer of zeste contains a region with sequence similarity to trithorax.

Molecular and Cellular Biology ◽

10.1128/mcb.13.10.6357 ◽

1993 ◽

Vol 13 (10) ◽

pp. 6357-6366 ◽

Cited By ~ 130

Author(s):

R S Jones ◽

W M Gelbart

Keyword(s):

Amino Acids ◽

Sequence Similarity ◽

Protein Product ◽

Polycomb Group ◽

Acute Leukemias ◽

Trithorax Group ◽

Acid Protein ◽

Enhancer Of Zeste ◽

Gene Enhancer ◽

Carboxy Terminal

As is typical of Polycomb-group loci, the Enhancer of zeste [E(z)] gene negatively regulates the segment identity genes of the Antennapedia (ANT-C) and Bithorax (BX-C) gene complexes. A second class of loci, collectively known as the trithorax group, plays an antagonistic role as positive regulators of the ANT-C and BX-C genes. Molecular analysis of the E(z) gene predicts a 760-amino-acid protein product. A region of 116 amino acids near the E(z) carboxy terminus is 41.2% identical (68.4% similar) with a carboxy-terminal region of the trithorax protein. This portion of the trithorax protein is part of a larger region previously shown to share extensive homology with a human protein (ALL-1/Hrx) that is implicated in acute leukemias. Over this same 116 amino acids, E(z) and ALL-1/Hrx are 43.9% identical (68.4% similar). Otherwise, E(z) is not significantly similar to any previously described proteins. As this region of sequence similarity is shared by two proteins with antagonistic functions, we suggest that it may comprise a domain that interacts with a common target, either nucleic acid or protein. Opposite effects on transcription might then be determined by other portions of the two proteins.

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Homeotic transformations of the axial skeleton of YY1 mutant mice and genetic interaction with the Polycomb group gene Ring1/Ring1A

Mechanisms of Development ◽

10.1016/j.mod.2006.02.003 ◽

2006 ◽

Vol 123 (4) ◽

pp. 312-320 ◽

Cited By ~ 19

Author(s):

Mar Lorente ◽

Claudia Pérez ◽

Carmen Sánchez ◽

Mary Donohoe ◽

Yang Shi ◽

...

Keyword(s):

Genetic Interaction ◽

Axial Skeleton ◽

Polycomb Group ◽

Mutant Mice ◽

Polycomb Group Gene

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Enhancer of Zeste Homolog 2 Overexpression Has a Role in the Development of Anaplastic Thyroid Carcinomas

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2010-1784 ◽

2011 ◽

Vol 96 (4) ◽

pp. 1029-1038 ◽

Cited By ~ 36

Author(s):

Eleonora Borbone ◽

Giancarlo Troncone ◽

Angelo Ferraro ◽

Zuzana Jasencakova ◽

Lovorka Stojic ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Anaplastic Thyroid Carcinoma ◽

Polycomb Group ◽

Migration And Invasion ◽

Polycomb Group Protein ◽

Expression Levels ◽

Thyroid Carcinomas ◽

Enhancer Of Zeste ◽

Pax8 Gene ◽

Group Protein

Abstract Context: Enhancer of zeste homolog 2 (EZH2) is a histone lysine methyltransferase belonging to the polycomb group protein family. Overexpression of EZH2 has been found in several human malignancies including hematological and solid tumors. Objectives: In this study we investigated the expression levels of EZH2 and its polycomb group protein partners in thyroid carcinoma tissues with different degrees of malignancy to identify potential new therapeutic targets for anaplastic thyroid carcinoma (ATC). Results: We show that high EZH2 expression levels are characteristic of undifferentiated ATC, whereas no significant changes were observed in well-differentiated papillary and follicular thyroid carcinomas as compared with normal thyroid. Knockdown of EZH2 in ATC cell lines results in cell growth inhibition, loss of anchorage-independent growth, migration, and invasion properties. Moreover, we demonstrate that EZH2 directly controls differentiation of ATC cells by silencing the thyroid specific transcription factor paired-box gene 8 (PAX8). Conclusions: EZH2 is specifically overexpressed in ATC, and it directly contributes to transcriptional silencing of PAX8 gene and ATC differentiation.

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