Epigenetic silencing of RNA polymerase I transcription: a role for DNA methylation and histone modification in nucleolar dominance

Zj, Chen; Pikaard, Craig S.

doi:10.1101/gad.11.16.2124

Cited by 350 publications

(277 citation statements)

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“…Pharmacological experiments with the HDAC inhibitor Trichostatin A (TSA) and the inhibitor of DNA methylation, 5-aza(deoxy)cytidine (5AZA) revealed, for example, that histone deacetylation and DNA methylation act synergistically to repress genes in Neurospora and in mammalian tumor cells (Selker, 1998;Momparler, 2003). Similar findings have been reported for silent plant rDNA genes in Arabidopsis or Brassica hybrids, where application of either inhibitor results in erasure of both repressive marks and gene reactivation (Chen and Pikaard, 1997;Lawrence et al, 2004). These reports are consistent with a model in which cytosine methylation and histone deacetylation crosstalk and are part of a self-reinforcing repressive cycle.…”

Section: Athda6: a Bridge Between Histone Acetylation And Dna Methylasupporting

confidence: 53%

Arabidopsis histone deacetylase 6: a green link to RNA silencing

et al. 2007

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Epigenetic reprogramming is at the base of cancer initiation and progression. Generally, genome-wide reduction in cytosine methylation contrasts with the hypermethylation of control regions of functionally wellestablished tumor suppressor genes and many other genes whose role in cancer biology is not yet clear. While insight into mechanisms that induce aberrant cytosine methylation in cancer cells is just beginning to emerge, the initiating signals for analogous promoter methylation in plants are well documented. In Arabidopsis, the silencing of promoters requires components of the RNA interference machinery and promoter double-stranded RNA (dsRNA) to induce a repressive chromatin state that is characterized by cytosine methylation and histone deacetylation catalysed by the RPD3-type histone deacetylase AtHDA6. Similar mechanisms have been shown to occur in fission yeast and mammals. This review focuses on the connections between cytosine methylation, dsRNA and AtHDA6-controlled histone deacetylation during promoter silencing in Arabidopsis and discusses potential mechanistic similarities of these silencing events in cancer and plant cells.

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Section: Athda6: a Bridge Between Histone Acetylation And Dna Methylasupporting

confidence: 53%

Arabidopsis histone deacetylase 6: a green link to RNA silencing

et al. 2007

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“…Resulting studies revealed that rRNA genes subjected to nucleolar dominance in Brassica or Arabidopsis allotetraploids can be derepressed by treatment with the histone deacetylase inhibitors sodium butyrate or trichostatin A (TSA), similar to the derepression observed upon treatment with aza-dC [39,40]. Significantly, no appreciable additivity or synergism between aza-dC and TSA occurs when plants are grown in the presence of both chemicals, indicating a partnership between DNA methylation and histone deacetylation within the same repression pathway.…”

Section: Concerted Changes In Dna Methylation and Histone Modificatiomentioning

confidence: 74%

“…Derepression of underdominant rRNA genes upon treatment with the histone deacetylase inhibitor TSA indicated a role for at least one histone deacetylase in nucleolar dominance [39]. The Arabidopsis genome contains 16 putative histone deacetylases, including 10 members of the RPD3/HDA1 family, four HDT family members, and two genes related to the yeast NAD dependent histone deacetylase Sir2p.…”

Section: Components Of the Rrna Gene Off Switch In Arabidopsismentioning

confidence: 99%

“…Collectively, these and other studies indicated a difference in the chromatin compaction of rRNA genes subjected to nucleolar dominance, but the role of DNA methylation in the process was unclear. Direct evidence that cytosine methylation plays a role in rRNA gene expression and nucleolar dominance came from simple experiments in which treatment with 5-aza-2'-deoxycytosine (aza-dC), a chemical inhibitor of cytosine methylation, caused the cytological reactivation of rye NORs in Triticale [38] and the transcriptional derepression of silent rRNA genes in Brassica [39] or Arabidopsis [40] allotetraploid hybrids.The fact that nucleolar dominance occurs in hybrids of Drosophila [41], which until recently were thought to lack genomic cytosine methylation entirely [42], suggested that DNA methylation alone was unlikely to explain nucleolar dominance in all organisms, prompting an investigation of histone modifications that might also play a role. Resulting studies revealed that rRNA genes subjected to nucleolar dominance in Brassica or Arabidopsis allotetraploids can be derepressed by treatment with the histone deacetylase inhibitors sodium butyrate or trichostatin A (TSA), similar to the derepression observed upon treatment with aza-dC [39,40].…”

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confidence: 99%

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rRNA gene silencing and nucleolar dominance: Insights into a chromosome-scale epigenetic on/off switch

Preuss

Pikaard

2007

Biochimica et Biophysica Acta (BBA) - Gene Structure and Expres

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135

105

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Ribosomal RNA (rRNA) gene transcription accounts for most of the RNA in prokaryotic and eukaryotic cells. In eukaryotes, there are hundreds (to thousands) of rRNA genes tandemly repeated head-to-tail within nucleolus organizer regions (NORs) that span millions of basepairs. These nucleolar rRNA genes are transcribed by RNA Polymerase I (Pol I) and their expression is regulated according to the physiological need for ribosomes. Regulation occurs at several levels, one of which is an epigenetic on/off switch that controls the number of active rRNA genes. Additional mechanisms then fine-tune transcription initiation and elongation rates to dictate the total amount of rRNA produced per gene. In this review, we focus on the DNA and histone modifications that comprise the epigenetic on/off switch. In both plants and animals, this system is important for controlling the dosage of active rRNA genes. The dosage control system is also responsible for the chromatinmediated silencing of one parental set of rRNA genes in genetic hybrids, a large-scale epigenetic phenomenon known as nucleolar dominance.Keywords epigenetic phenomena; RNA polymerase I; DNA methylation; cytosine methylation; histone methylation; histone deacetylation; histone deacetylase; transcription; ribosomal RNA; nucleolus; nucleolus organizer region Large scale cytological effects of rRNA gene regulation: nucleolus and secondary constriction formationThe most prominent feature of a eukaryotic nucleus during interphase is the nucleolus (Figure 1), a region that contains relatively little chromosomal DNA but is rich in RNAs, proteins and ribonucleoprotein particles, including the large and small ribosome subunits as they undergo assembly [1][2][3]. The location of a nucleolus is not determined randomly; instead its formation is determined by the position of a discrete chromosomal locus known as a nucleolus organizer region, or NOR [4]. This fact was discovered based on an intriguing property: upon condensation of chromosomes at metaphase, NORs fail to condense to the same extent as surrounding chromosomal sequences and thus give rise to "secondary constrictions", with "primary constrictions" being defined as the centromeres (see Figure 1). Heitz initially noted that nucleoli form at, or very near, the sites of secondary constrictions [5] and McClintock soon thereafter obtained direct evidence [6]. She identified a maize line in which a chromosome break at or near the secondary constriction on chromosome 9, followed by translocation of one *Author to whom correspondence should be addressed: pikaard@biology2.wustl.edu, phone: Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the conte...

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“…(78,80) Silenced rRNA genes in Arabidopsis and Brassica allotetraploids were reactivated by chemical inhibitors for DNA methylation and/or histone deacetylation, suggesting that rRNA genes are silenced by DNA and histone modifications presumably associated with inactive chromatin structure. (81) Collectively, the data suggest that rRNA gene silencing acts on chromosomal loci that result in cooperative silencing of rRNA genes. (21) How are orthologous protein-coding genes regulated in synthetic interspecific hybrids and allotetraploids?…”

Section: Activation Of Transposons and Changes In Dna Methylation In mentioning

confidence: 97%

Mechanisms of genomic rearrangements and gene expression changes in plant polyploids

2006

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SummaryPolyploidy is produced by multiplication of a single genome (autopolyploid) or combination of two or more divergent genomes (allopolyploid). The available data obtained from the study of synthetic (newly created or human-made) plant allopolyploids have documented dynamic and stochastic changes in genomic organization and gene expression, including sequence elimination, inter-chromosomal exchanges, cytosine methylation, gene repression, novel activation, genetic dominance, subfunctionalization and transposon activation. The underlying mechanisms for these alterations are poorly understood. To promote a better understanding of genomic and gene expression changes in polyploidy, we briefly review origins and forms of polyploidy and summarize what has been learned from genome-wide gene expression analyses in newly synthesized autoand allopolyploids. We show transcriptome divergence between the progenitors and in the newly formed allopolyploids. We propose models for transcriptional regulation, chromatin modification and RNA-mediated pathways in establishing locus-specific expression of orthologous and homoeologous genes during allopolyploid formation and evolution. Polyploidy and its formsPolyploidy occurs throughout the evolutionary history of all eukaryotes, (1,2) predominately in flowering plants (3,4) including many important agricultural crops. (5) Compared to plants, polyploidy occurs rarely in animals, but clearly exists in some invertebrates (e.g. insects) and vertebrates (e.g. fish, amphibians and reptiles). (4,6) The relative paucity of polyploidy in animals is attributed to the delicate schemes of sex determination and animal development, which are disrupted by polyploidization. (7,8) Therefore, polyploid animals rarely exist. (9) Moreover, aneuploid and polyploid cells in animals and human are often associated with malignant cell proliferation or carcinogenesis. (10) However, endopolyploidy (somatic polyploid cells within a diploid individual) appears to be a physiological response to developmental changes in plants and some animals, (11,12) indicating plasticity of plant and animal genomes. In the post-sequencing era, polyploidy is proving to be a fascinating and challenging field of plant biology, stimulating many research advances and insightful reviews. (2,13 -24) Here we attempt to update the views using genomic-scale results and provide new mechanistic insights.Historically, Winkler (1916) introduced the term polyploidy, (25) and Winge (1917) called attention to the general importance of polyploidy in the evolution of angiosperms. (26) At that time, research in polyploidy was somewhat limited by the plant and animal materials that were available in nature. In 1937, Blakeslee and Avery induced polyploidy in plants using colchicine, a chemical inhibitor of mitotic cell divisions. (27) The technique has been successfully used to induce chromosome doubling in meristemic cells of diploids and interspecific hybrids. Doubling a single 'diploid' genome results in an autotetraploid, while doubling c...

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Epigenetic silencing of RNA polymerase I transcription: a role for DNA methylation and histone modification in nucleolar dominance

Cited by 350 publications

References 106 publications

Arabidopsis histone deacetylase 6: a green link to RNA silencing

Arabidopsis histone deacetylase 6: a green link to RNA silencing

rRNA gene silencing and nucleolar dominance: Insights into a chromosome-scale epigenetic on/off switch

Mechanisms of genomic rearrangements and gene expression changes in plant polyploids

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