6jnn

REF6 ZnF2-4-NAC004-mC1 complexREF6 ZnF2-4-NAC004-mC1 complex

Structural highlights

6jnn is a 12 chain structure with sequence from Arabidopsis thaliana and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

REF6_ARATH Histone demethylase that demethylates 'Lys-27' (H3K27me) of histone H3. Demethylates both tri- (H3K27me3) and di-methylated (H3K27me2) H3K27me (PubMed:21642989, PubMed:27111035). Demethylates also H3K4me3/2 and H3K36me3/2 in an in vitro assay (PubMed:20711170). Involved in the transcriptional regulation of hundreds of genes regulating developmental patterning and responses to various stimuli (PubMed:18467490). Binds DNA via its four zinc fingers in a sequence-specific manner, 5'-CTCTGYTY-3', to promote the demethylation of H3K27me3 and the regulation of organ boundary formation (PubMed:27111034, PubMed:27111035). Involved in the regulation of flowering time by repressing FLOWERING LOCUS C (FLC) expression (PubMed:15377760). Interacts with the NF-Y complexe to regulate SOC1 (PubMed:25105952). Mediates the recruitment of BRM to its target loci (PubMed:27111034).^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

Publication Abstract from PubMed

RELATIVE OF EARLY FLOWERING 6 (REF6/JMJ12), a Jumonji C (JmjC)-domain-containing H3K27me3 histone demethylase, finds its target loci in Arabidopsis genome by directly recognizing the CTCTGYTY motif via its zinc-finger (ZnF) domains. REF6 tends to bind motifs located in active chromatin states that are depleted for heterochromatic modifications. However, the underlying mechanism remains unknown. Here, we show that REF6 preferentially bind to hypo-methylated CTCTGYTY motifs in vivo, and that CHG methylation decreases REF6 DNA binding affinity in vitro. In addition, crystal structures of ZnF-clusters in complex with DNA oligonucleotides reveal that 5-methylcytosine is unfavorable for REF6 binding. In drm1 drm2 cmt2 cmt3 (ddcc) quadruple mutants, in which non-CG methylation is significantly reduced, REF6 can ectopically bind a small number of new target loci, most of which are located in or neighbored with short TEs in euchromatic regions. Collectively, our findings reveal that DNA methylation, likely acting in combination with other epigenetic modifications, may partially explain why REF6 binding is depleted in heterochromatic loci.

DNA methylation repels targeting of Arabidopsis REF6.,Qiu Q, Mei H, Deng X, He K, Wu B, Yao Q, Zhang J, Lu F, Ma J, Cao X Nat Commun. 2019 May 2;10(1):2063. doi: 10.1038/s41467-019-10026-1. PMID:31048693^[8]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Noh B, Lee SH, Kim HJ, Yi G, Shin EA, Lee M, Jung KJ, Doyle MR, Amasino RM, Noh YS. Divergent roles of a pair of homologous jumonji/zinc-finger-class transcription factor proteins in the regulation of Arabidopsis flowering time. Plant Cell. 2004 Oct;16(10):2601-13. doi: 10.1105/tpc.104.025353. Epub 2004 Sep, 17. PMID:15377760 doi:http://dx.doi.org/10.1105/tpc.104.025353
↑ Yu X, Li L, Li L, Guo M, Chory J, Yin Y. Modulation of brassinosteroid-regulated gene expression by Jumonji domain-containing proteins ELF6 and REF6 in Arabidopsis. Proc Natl Acad Sci U S A. 2008 May 27;105(21):7618-23. doi:, 10.1073/pnas.0802254105. Epub 2008 May 8. PMID:18467490 doi:http://dx.doi.org/10.1073/pnas.0802254105
↑ Ko JH, Mitina I, Tamada Y, Hyun Y, Choi Y, Amasino RM, Noh B, Noh YS. Growth habit determination by the balance of histone methylation activities in Arabidopsis. EMBO J. 2010 Sep 15;29(18):3208-15. doi: 10.1038/emboj.2010.198. Epub 2010 Aug, 13. PMID:20711170 doi:http://dx.doi.org/10.1038/emboj.2010.198
↑ Lu F, Cui X, Zhang S, Jenuwein T, Cao X. Arabidopsis REF6 is a histone H3 lysine 27 demethylase. Nat Genet. 2011 Jun 5;43(7):715-9. doi: 10.1038/ng.854. PMID:21642989 doi:http://dx.doi.org/10.1038/ng.854
↑ Hou X, Zhou J, Liu C, Liu L, Shen L, Yu H. Nuclear factor Y-mediated H3K27me3 demethylation of the SOC1 locus orchestrates flowering responses of Arabidopsis. Nat Commun. 2014 Aug 8;5:4601. doi: 10.1038/ncomms5601. PMID:25105952 doi:http://dx.doi.org/10.1038/ncomms5601
↑ Li C, Gu L, Gao L, Chen C, Wei CQ, Qiu Q, Chien CW, Wang S, Jiang L, Ai LF, Chen CY, Yang S, Nguyen V, Qi Y, Snyder MP, Burlingame AL, Kohalmi SE, Huang S, Cao X, Wang ZY, Wu K, Chen X, Cui Y. Concerted genomic targeting of H3K27 demethylase REF6 and chromatin-remodeling ATPase BRM in Arabidopsis. Nat Genet. 2016 Jun;48(6):687-93. doi: 10.1038/ng.3555. Epub 2016 Apr 25. PMID:27111034 doi:http://dx.doi.org/10.1038/ng.3555
↑ Cui X, Lu F, Qiu Q, Zhou B, Gu L, Zhang S, Kang Y, Cui X, Ma X, Yao Q, Ma J, Zhang X, Cao X. REF6 recognizes a specific DNA sequence to demethylate H3K27me3 and regulate organ boundary formation in Arabidopsis. Nat Genet. 2016 Jun;48(6):694-9. doi: 10.1038/ng.3556. Epub 2016 Apr 25. PMID:27111035 doi:http://dx.doi.org/10.1038/ng.3556
↑ Qiu Q, Mei H, Deng X, He K, Wu B, Yao Q, Zhang J, Lu F, Ma J, Cao X. DNA methylation repels targeting of Arabidopsis REF6. Nat Commun. 2019 May 2;10(1):2063. doi: 10.1038/s41467-019-10026-1. PMID:31048693 doi:http://dx.doi.org/10.1038/s41467-019-10026-1

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Noh B, Lee SH, Kim HJ, Yi G, Shin EA, Lee M, Jung KJ, Doyle MR, Amasino RM, Noh YS. Divergent roles of a pair of homologous jumonji/zinc-finger-class transcription factor proteins in the regulation of Arabidopsis flowering time. Plant Cell. 2004 Oct;16(10):2601-13. doi: 10.1105/tpc.104.025353. Epub 2004 Sep, 17. PMID:15377760 doi:http://dx.doi.org/10.1105/tpc.104.025353

[2] Yu X, Li L, Li L, Guo M, Chory J, Yin Y. Modulation of brassinosteroid-regulated gene expression by Jumonji domain-containing proteins ELF6 and REF6 in Arabidopsis. Proc Natl Acad Sci U S A. 2008 May 27;105(21):7618-23. doi:, 10.1073/pnas.0802254105. Epub 2008 May 8. PMID:18467490 doi:http://dx.doi.org/10.1073/pnas.0802254105

[3] Ko JH, Mitina I, Tamada Y, Hyun Y, Choi Y, Amasino RM, Noh B, Noh YS. Growth habit determination by the balance of histone methylation activities in Arabidopsis. EMBO J. 2010 Sep 15;29(18):3208-15. doi: 10.1038/emboj.2010.198. Epub 2010 Aug, 13. PMID:20711170 doi:http://dx.doi.org/10.1038/emboj.2010.198

[4] Lu F, Cui X, Zhang S, Jenuwein T, Cao X. Arabidopsis REF6 is a histone H3 lysine 27 demethylase. Nat Genet. 2011 Jun 5;43(7):715-9. doi: 10.1038/ng.854. PMID:21642989 doi:http://dx.doi.org/10.1038/ng.854

[5] Hou X, Zhou J, Liu C, Liu L, Shen L, Yu H. Nuclear factor Y-mediated H3K27me3 demethylation of the SOC1 locus orchestrates flowering responses of Arabidopsis. Nat Commun. 2014 Aug 8;5:4601. doi: 10.1038/ncomms5601. PMID:25105952 doi:http://dx.doi.org/10.1038/ncomms5601

[6] Li C, Gu L, Gao L, Chen C, Wei CQ, Qiu Q, Chien CW, Wang S, Jiang L, Ai LF, Chen CY, Yang S, Nguyen V, Qi Y, Snyder MP, Burlingame AL, Kohalmi SE, Huang S, Cao X, Wang ZY, Wu K, Chen X, Cui Y. Concerted genomic targeting of H3K27 demethylase REF6 and chromatin-remodeling ATPase BRM in Arabidopsis. Nat Genet. 2016 Jun;48(6):687-93. doi: 10.1038/ng.3555. Epub 2016 Apr 25. PMID:27111034 doi:http://dx.doi.org/10.1038/ng.3555

[7] Cui X, Lu F, Qiu Q, Zhou B, Gu L, Zhang S, Kang Y, Cui X, Ma X, Yao Q, Ma J, Zhang X, Cao X. REF6 recognizes a specific DNA sequence to demethylate H3K27me3 and regulate organ boundary formation in Arabidopsis. Nat Genet. 2016 Jun;48(6):694-9. doi: 10.1038/ng.3556. Epub 2016 Apr 25. PMID:27111035 doi:http://dx.doi.org/10.1038/ng.3556

[8] Qiu Q, Mei H, Deng X, He K, Wu B, Yao Q, Zhang J, Lu F, Ma J, Cao X. DNA methylation repels targeting of Arabidopsis REF6. Nat Commun. 2019 May 2;10(1):2063. doi: 10.1038/s41467-019-10026-1. PMID:31048693 doi:http://dx.doi.org/10.1038/s41467-019-10026-1

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]