Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription

Zilberman, Daniel; Gehring, Mary; Tran, Robert K.; Ballinger, Tracy; Henikoff, Steven

doi:10.1038/ng1929

Cited by 1,257 publications

(1,311 citation statements)

References 41 publications

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“…Although the level of cytosine methylation is quite similar in all 10 Arabidopsis ChCs (18,19), AtMBD5 and AtMBD6 accumulate mostly at only two ChCs adjacent to the nucleolus. This suggests that besides the mCpGbinding activity of the MBD motif, additional factors participate in recruiting AtMBD proteins to mCpG chromosomal sites.…”

Section: Resultsmentioning

confidence: 92%

The Three Methyl-CpG-binding Domains of AtMBD7 Control Its Subnuclear Localization and Mobility

Zemach

Gaspan

Grafi

2008

Journal of Biological Chemistry

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Three methyl-CpG-binding domain (MBD) proteins in Arabidopsis, AtMBD5, AtMBD6, and AtMBD7, are functional in binding methylated CpG dinucleotides in vitro and localize to the highly CpG-methylated chromocenters in vivo. These proteins differ, however, in their subnuclear localization pattern; AtMBD5 and AtMBD6, each containing a single MBD motif, show preference for two perinucleolar chromocenters, whereas AtMBD7, a naturally occurring poly-MBD protein containing three MBD motifs, localizes to all chromocenters. Here we studied the significance of multiple MBD motifs for subnuclear localization and mobility in living cells. We found that the number of MBD motifs determines the subnuclear localization of the MBD protein. Furthermore, live kinetic experiments showed that AtMBD7-green fluorescent protein (GFP) has lower mobility than AtMBD5-GFP and AtMBD6-GFP, which is conferred by cooperative activity of its three MBD motifs. Thus, the number of MBD motifs appears to affect not only binding affinity and mobility within the nucleus, but also the subnuclear localization of the protein. Our results suggest that poly-MBD proteins can directly affect chromatin structure by inducing intra-and interchromatin compaction via bridging over multiple methylated CpG sites.Cytosine methylation is a common epigenetic modification of most eukaryotic nuclear DNA. Intensive studies demonstrated the central role played by cytosine methylation in genome organization, gene expression, and growth and development. The way by which the methyl group is interpreted into a functional state has begun to be unraveled with the isolation and characterization of methylated DNA-binding proteins. This group of proteins includes an evolutionary conserved protein family, initially described in animals, termed methyl-CpGbinding domain (MBD) 2 proteins (1). Biochemical and molecular analyses suggest that mammalian MBDs induce the formation of a repressive chromatin structure at methylated CpG (mCpG) sites by the recruitment of various chromatin factors including histone deacetylases, histone methyltransferases, and ATPase-dependent nucleosome remodeling factors (2, 3). Thus far, of the 13 AtMBD proteins found in Arabidopsis, only AtMBD5, AtMBD6, and AtMBD7 were found to bind mCpG sites in vitro and to localize in vivo to the highly methylated chromocenters (ChCs) (reviewed in Refs. 4 and 5). This chromocenter localization is CpG methylation-dependent inasmuch as it was disrupted in the hypomethylated mutants ddm1 and met1 (6). Yet, these three AtMBDs display different localization patterns within Arabidopsis nuclei; AtMBD7 is predominantly localized at all ChCs, whereas AtMBD5 and AtMBD6 show preference for two perinucleolar ChCs adjacent to the ribosomal DNA clusters (6). A major structural feature distinguishing AtMBD7 from AtMBD5 and AtMBD6 is the presence of three MBD motifs within its protein sequence. Notably, naturally occurring poly-MBD proteins appear to be unique to plants as to date no such protein has been found in animals. Here we studied...

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Section: Resultsmentioning

confidence: 92%

The Three Methyl-CpG-binding Domains of AtMBD7 Control Its Subnuclear Localization and Mobility

Zemach

Gaspan

Grafi

2008

Journal of Biological Chemistry

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“…In this study, the methylation of the "CpG4" locus may prevent the binding of USF to the promoter region of galectin, and up-regulate the gene expression. DNA methylation is only one of the factors that may influence the mRNA expression [38]. The mechanism of expression level changes of galectin gene during the mantle wound healing process need to be further elucidated.…”

Section: Cpg1mentioning

confidence: 99%

DNA methylation is associated with expression level changes of galectin gene in mantle wound healing process of pearl oyster, Pinctada fucata

Huang

Guan

et al. 2015

Fish & Shellfish Immunology

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“…Peculiarities of DNA structure, such as pyrimidine richness coupled to the formation of hairpin structures, have been discussed as potential features that might attract aberrant methylation at these genes, but this does not explain why methylation is only induced in the situation of global hypomethylation. One alternative mechanism is possibly the reduction of genic CpG methylation, which occurs within transcribed sequences at an unexpectedly high frequency in Arabidopsis and has been discussed to suppress the activity of cryptic AtHDA6 controls dsRNA-induced repressive chromatin W Aufsatz et al promoters (Tran et al, 2005;Zhang et al, 2006;Zilberman et al, 2007). Reduction of gene body methylation might result in activation of cryptic antisense promoters, whose activity would result in the formation of regional dsRNA that, in turn, could trigger aberrant de novo methylation by an RdDM-like mechanism.…”

Section: Multiple Ways Of Recruiting Athda6?mentioning

confidence: 99%

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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Genome-wide analysis of Arabidopsis thaliana DNA methylation uncovers an interdependence between methylation and transcription

Cited by 1,257 publications

References 41 publications

The Three Methyl-CpG-binding Domains of AtMBD7 Control Its Subnuclear Localization and Mobility

The Three Methyl-CpG-binding Domains of AtMBD7 Control Its Subnuclear Localization and Mobility

DNA methylation is associated with expression level changes of galectin gene in mantle wound healing process of pearl oyster, Pinctada fucata

Arabidopsis histone deacetylase 6: a green link to RNA silencing

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