Transcriptional repression activity of PAX3 is modulated by competition between corepressor KAP1 and heterochromatin protein 1

2006 ◽  
Vol 349 (2) ◽  
pp. 573-581 ◽  
Author(s):  
Mei-Ju Hsieh ◽  
Ya-Li Yao ◽  
I-Lu Lai ◽  
Wen-Ming Yang
Keyword(s):  
Transcriptional Repression ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein

scholarly journals CSIG-27. PRC2-INDEPENDENT FUNCTION OF EZH2/HP1BP3 COMPLEX IN GLIOMA STEM CELLS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi49-vi50
Author(s):  
Junxia Zhang ◽  
Tianfu Yu ◽  
Ning Liu
Keyword(s):  
Stem Cells ◽  
Transcriptional Repression ◽  
Glioma Stem Cells ◽  
Independent Function ◽  
Set Domain ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Histone Lysine Methyltransferase ◽  
Lysine Methyltransferase

Abstract Glioblastoma (GBM) displays cellular and genetical heterogeneity harboring a subpopulation of glioma stem cells (GSCs). Enhancer of zeste homolog 2 (EZH2), a histone lysine methyltransferase, is the core subunit of the polycomb repressor 2 (PRC2) complex, mediates gene transcriptional repression in both normal and tumor stem cells. An oncogenic role of EZH2 as a PRC2-dependent transcriptional silencer is well established; however, non-canonical functions of EZH2 are incompletely understood. Here we found a novel oncogenic mechanism for EZH2 in a PRC2-indenpend way in GSCs. Using HPLC-MS/MS and IP assay, EZH2 bound to HP1BP3 (heterochromatin protein 1 binding protein 3), a heterochromatin-related protein, with its pre-SET domain. Overexpression of H1P3B3 enhanced the proliferation, self-renewal and temozolomide (TMZ) resistance of GBM cells. Intriguingly, H1PBP3 was up-regulated in high grade gliomas with proneural (PN) subtypes and had a high predictive value on prognosis in patients with PN gliomas. Furthermore, EZH2 and HP1BP3 co-activated the expression of WNT7B by blocking the methylation of H3K9, thereby increasing TMZ resistance and tumorigenicity of glioblastoma cells. Interestingly, inhibition of WNT7B autocrine via LGK974, a specific porcupine inhibitor, effectively reversed the TMZ resistance of both GSCs and GBM glioma cells expressing HP1BP3. Hence, targeting the PRC2-independent function of EZH2 is an effective approach to enhance the efficacy of treating GBM.

scholarly journals Is HP1 an RNA detector that functions both in repression and activation?

2003 ◽  
Vol 161 (4) ◽  
pp. 671-672 ◽  
Author(s):  
Rebecca Kellum
Keyword(s):  
Transcriptional Repression ◽  
Polytene Chromosomes ◽  
Pericentric Heterochromatin ◽  
Original Study ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Genetic Studies ◽  
Transcript Levels ◽  
Cytological Features ◽  
Initial Discovery

Heterochromatin is defined as regions of compact chromatin that persist throughout the cell cycle (Heitz, 1928). The earliest cytological observations of heterochromatin were followed by ribonucleotide labeling experiments that showed it to be transcriptionally inert relative to the more typical euchromatic regions that decondense during interphase. Genetic studies of rearrangements that place euchromatic genes next to blocks of heterochromatin also pointed out the repressive nature of heterochromatin (Grigliatti, 1991; and references therein). The discovery of the heterochromatin-enriched protein heterochromatin protein 1 (HP1)**Abbreviation used in this paper: HP1, heterochromatin protein 1. by Elgin and co-workers in the mid-1980s suggested that the distinct cytological features of this chromatin may be related to its unique nucleoprotein composition (James and Elgin, 1986; James et al., 1989). HP1 immunostaining on polytene chromosomes from Drosophila larval salivary glands was used to show enrichment of the protein in pericentric heterochromatin. Since that initial discovery, HP1 homologues have been found in species ranging from fission yeast to humans where it is associated with gene silencing (Eissenberg and Elgin, 2000; and references therein). A number of euchromatic sites of localization were also reported in this original study. It has been generally assumed that these sites might constitute euchromatic sites of transcriptional repression by HP1. Indeed, several genes located at one of these sites (cytological region 31) have increased transcript levels in mutants for HP1 (Hwang et al., 2001).

scholarly journals Disruption of the Interaction between Transcriptional Intermediary Factor 1β and Heterochromatin Protein 1 Leads to a Switch from DNA Hyper- to Hypomethylation and H3K9 to H3K27 Trimethylation on the MEST Promoter Correlating with Gene Reactivation

2009 ◽  
Vol 20 (1) ◽  
pp. 296-305 ◽  
Author(s):  
Raphaël Riclet ◽  
Mariam Chendeb ◽  
Jean-Luc Vonesch ◽  
Dirk Koczan ◽  
Hans-Juergen Thiesen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Transcriptional Repression ◽  
Promoter Region ◽  
Loss Of Function ◽  
Dna Hypomethylation ◽  
Dna Hypermethylation ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
H3k27 Trimethylation ◽  
H3k9 Trimethylation

Here, we identified the imprinted mesoderm-specific transcript (MEST) gene as an endogenous TIF1β primary target gene and demonstrated that transcriptional intermediary factor (TIF) 1β, through its interaction with heterochromatin protein (HP) 1, is essential in establishing and maintaining a local heterochromatin-like structure on MEST promoter region characterized by H3K9 trimethylation and hypoacetylation, H4K20 trimethylation, DNA hypermethylation, and enrichment in HP1 that correlates with preferential association to foci of pericentromeric heterochromatin and transcriptional repression. On disruption of the interaction between TIF1β and HP1, TIF1β is released from the promoter region, and there is a switch from DNA hypermethylation and histone H3K9 trimethylation to DNA hypomethylation and histone H3K27 trimethylation correlating with rapid reactivation of MEST expression. Interestingly, we provide evidence that the imprinted MEST allele DNA methylation is insensitive to TIF1β loss of function, whereas the nonimprinted allele is regulated through a distinct TIF1β–DNA methylation mechanism.

scholarly journals Relationship between Histone H3 Lysine 9 Methylation, Transcription Repression, and Heterochromatin Protein 1 Recruitment

2005 ◽  
Vol 25 (7) ◽  
pp. 2525-2538 ◽  
Author(s):  
M. David Stewart ◽  
Jiwen Li ◽  
Jiemin Wong
Keyword(s):  
Transcriptional Repression ◽  
Associated Factors ◽  
Specific Binding ◽  
Histone H3 ◽  
Histone Deacetylation ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Histone Methyltransferases ◽  
Protein Protein Interaction ◽  
The Relationship

ABSTRACT Histone H3 lysine 9 (H3-K9) methylation has been shown to correlate with transcriptional repression and serve as a specific binding site for heterochromatin protein 1 (HP1). In this study, we investigated the relationship between H3-K9 methylation, transcriptional repression, and HP1 recruitment by comparing the effects of tethering two H3-K9-specific histone methyltransferases, SUV39H1 and G9a, to chromatin on transcription and HP1 recruitment. Although both SUV39H1 and G9a induced H3-K9 methylation and repressed transcription, only SUV39H1 was able to recruit HP1 to chromatin. Targeting HP1 to chromatin required not only K9 methylation but also a direct protein-protein interaction between SUV39H1 and HP1. Targeting methyl-K9 or a HP1-interacting region of SUV39H1 alone to chromatin was not sufficient to recruit HP1. We also demonstrate that methyl-K9 can suppress transcription independently of HP1 through a mechanism involving histone deacetylation. In an effort to understand how H3-K9 methylation led to histone deacetylation in both H3 and H4, we found that H3-K9 methylation inhibited histone acetylation by p300 but not its association with chromatin. Collectively, these data indicate that H3-K9 methylation alone can suppress transcription but is insufficient for HP1 recruitment in the context of chromatin exemplifying the importance of chromatin-associated factors in reading the histone code.

scholarly journals BRD4 facilitates DNA damage response and represses CBX5/Heterochromatin protein 1 (HP1)

Oncotarget ◽  
2017 ◽  
Vol 8 (31) ◽  
pp. 51402-51415 ◽  
Author(s):  
Georgios Pongas ◽  
Marianne K. Kim ◽  
Dong J. Min ◽  
Carrie D. House ◽  
Elizabeth Jordan ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Heterochromatin Protein 1 ◽  
Heterochromatin Protein ◽  
Damage Response
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