Active DNA demethylation by oxidation and repair

Gong, Zhizhong; Zhu, Jian‐Kang

doi:10.1038/cr.2011.140

Cited by 56 publications

(48 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TDG Is Up-regulated in CRC-Recently, several enzymes involved in active DNA demethylation were identified (15)(16)(17). To understand the functions of these genes in CRC, we analyzed the expression of these genes in CRC cell lines and human tissues.…”

Section: Resultsmentioning

confidence: 99%

“…TDG also plays essential roles in epigenetic regulation. It interacts with activation-induced deaminase and the non-enzyme factor Gadd45 (growth-arrested and DNA damage-induced protein 45) and works with 5-methylcytosine hydroxylases TETs (ten-eleven translocation) to regulate active DNA demethylation (15)(16)(17). In addition to its function in DNA modification, TDG interacts with several transcription factors, including thyroid transcription factor 1 (TTF-1) (18), estrogen receptor (ER␣) (19), retinoic acid receptor (RAR) and retinoid X receptor (RXR) (20).…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

See 1 more Smart Citation

Thymine DNA Glycosylase Is a Positive Regulator of Wnt Signaling in Colorectal Cancer

Shi

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

Thymine DNA Glycosylase Is a Positive Regulator of Wnt Signaling in Colorectal Cancer

Shi

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Active DNA demethylation is carried out by DNA demethylases in the ROS1 protein family through a base excision-repair pathway (Zhu, 2009;Gong and Zhu, 2011). However, how these DNA demethylases are recruited to the specific target regions for removal of DNA methylation is not known.…”

Section: Discussionmentioning

confidence: 99%

Methyl-CpG-Binding Domain Protein MBD7 Is Required for Active DNA Demethylation in Arabidopsis

Wang¹,

Dong

Jin³

et al. 2015

Plant Physiology

Self Cite

View full text Add to dashboard Cite

Although researchers have established that DNA methylation and active demethylation are dynamically regulated in plant cells, the molecular mechanism for the regulation of active DNA demethylation is not well understood. By using an Arabidopsis (Arabidopsis thaliana) line expressing the Promoter RESPONSIVE TO DEHYDRATION 29A:LUCIFERASE (ProRD29A:LUC) and Promoter cauliflower mosaic virus 35S:NEOMYCIN PHOSPHOTRANSFERASE II (Pro35S:NPTII) transgenes, we isolated an mbd7 (for methyl-CpG-binding domain protein7) mutant. The mbd7 mutation causes an inactivation of the Pro35S:NPTII transgene but does not affect the expression of the ProRD29A:LUC transgene. The silencing of the Pro35S:NPTII reporter gene is associated with DNA hypermethylation of the reporter gene. MBD7 interacts physically with REPRESSOR OF SILENCING5/INCREASED DNA METHYLATION2, a protein in the small heat shock protein family. MBD7 prefers to target the genomic loci with high densities of DNA methylation around chromocenters. The Gypsy-type long terminal repeat retrotransposons mainly distributed around chromocenters are most affected by mbd7 in all transposons. Our results suggest that MBD7 is required for active DNA demethylation and antisilencing of the genomic loci with high densities of DNA methylation in Arabidopsis.

show abstract

“…DNA methylation tends to increase heterochromatin status and silence genes. Active DNA demethylation is an important mechanism for maintaining gene activity in both plants and animals (24). In this study, we characterized a PHD finger-containing protein that binds to H3K4me0 and suppresses gene silencing caused by DNA methylation.…”

Section: Ros4 Is Required For the Expression Of 35s-nptii Even When Dnamentioning

confidence: 99%

Antisilencing role of the RNA-directed DNA methylation pathway and a histone acetyltransferase in Arabidopsis

Qian

Zhao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

REPRESSOR OF SILENCING 1 (ROS1) is a DNA demethylation enzyme that was previously identified during a genetic screen for the silencing of both RD29A-LUC and 35S-NPTII transgenes on a T-DNA construct. Here we performed a genetic screen to identify additional mutants in which the 35S-NPTII transgene is silenced. We identified several alleles of ros1 and of the following components of the RNA-directed DNA methylation (RdDM) pathway: NRPD1 (the largest subunit of polymerase IV), RDR2, NRPE1 (the largest subunit of polymerase V), NRPD2, AGO4, and DMS3. Our results show that the silencing of 35S-NPTII in the RdDM pathway mutants is due to the reduced expression of ROS1 in the mutants. We also identified a putative histone acetyltransferase (ROS4) from the genetic screen. The acetyltransferase contains a PHD-finger domain that binds to unmethylated histone H3K4. The mutation in ROS4 led to reduction of H3K18 and H3K23 acetylation levels. We show that the silencing of 35S-NPTII and some transposable element genes was released by the ddm1 mutation but that this also required ROS4. Our study identifies a unique antisilencing factor, and reveals that the RdDM pathway has an antisilencing function due to its role in maintaining ROS1 expression.transcriptional gene silencing | epigenetic | gene silencing | histone modification D NA cytosine methylation is an important epigenetic modification in plants and animals. The molecular mechanism for RNA-directed DNA methylation (RdDM) has been well-established by both genetic and biochemical studies in Arabidopsis (1-4). Small RNAs (∼24 bp) and long noncoding RNAs produced by a complex transcriptional machinery composed of polymerase (Pol) IV and Pol V, together with other proteins, target specific sequences for de novo DNA methylation (1-4). RdDM mainly occurs in transposons, retrotransposons, rDNA arrays, and centromeric repeat regions, and accounts for about 30% of the DNA methylation in the genome of Arabidopsis (5, 6).DNA methylation can be removed passively during DNA replication or actively by the DNA glycosylase REPRESSOR OF SILENCING 1 (ROS1) and its homologs DEMETER (DME), DEMETER-LIKE 2 (DML2), and DML3 (1, 2, 7, 8). ROS1 was identified in a genetic screen in which the originally active RD29A-LUC was silenced in ros1 mutants (9). ROS1 is a key DNA demethylation component in vegetative tissues (9), and its transcript level is regulated by MET1 and several RdDM components (10). Screening for second-site suppressors of ros1 mutants by using silenced RD29A-LUC has enabled researchers to identify the main components of the RdDM pathway and has further indicated that RdDM and ROS1 antagonistically regulate DNA methylation (11)(12)(13)(14).ros1 mutations also cause the silencing of another transgene, 35S-NPTII, which is in the same T-DNA construct as RD29A-LUC (9). RD29A-LUC has been used to identify ROS1 and ROS3 genes (9, 15). By screening for second-site suppressors of ros1 using silenced 35S-NPTII, we previously identified genes that are involved in DNA replication and maint...

show abstract

Active DNA demethylation by oxidation and repair

Cited by 56 publications

References 19 publications

Thymine DNA Glycosylase Is a Positive Regulator of Wnt Signaling in Colorectal Cancer

Thymine DNA Glycosylase Is a Positive Regulator of Wnt Signaling in Colorectal Cancer

Methyl-CpG-Binding Domain Protein MBD7 Is Required for Active DNA Demethylation in Arabidopsis

Antisilencing role of the RNA-directed DNA methylation pathway and a histone acetyltransferase in Arabidopsis

Contact Info

Product

Resources

About