| Structural highlights
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 Flowing 6 (REF6) is a DNA-sequence-specific H3K27me3/2 demethylase that contains four zinc finger (ZnF) domains and targets several thousand genes in Arabidopsis thaliana. The ZnF domains are essential for binding target genes, but the structural basis remains unclear. Here, we determined crystal structures of the ZnF domains and REF6-DNA complex, revealing a unique REF6-family-specific half-cross-braced ZnF (RCZ) domain and two C2H2-type ZnFs. DNA-binding induces a profound conformational change in the hinge region of REF6. Each REF6 recognizes six bases and DNA methylation reduces the binding affinity. Both the acidic region and basic region are important for the self-association of REF6. The REF6 DNA-binding affinity is determined by the sequence-dependent conformations of DNA and also the cooperativity in different target motifs. The conformational plasticity enables REF6 to function as a global transcriptional regulator that directly binds to many diverse genes, revealing the structural basis for the epigenetic modification recognition.
Crystal structures of REF6 and its complex with DNA reveal diverse recognition mechanisms.,Tian Z, Li X, Li M, Wu W, Zhang M, Tang C, Li Z, Liu Y, Chen Z, Yang M, Ma L, Caba C, Tong Y, Lam HM, Dai S, Chen Z Cell Discov. 2020 Mar 31;6:17. doi: 10.1038/s41421-020-0150-6. eCollection 2020. PMID:32257379[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Tian Z, Li X, Li M, Wu W, Zhang M, Tang C, Li Z, Liu Y, Chen Z, Yang M, Ma L, Caba C, Tong Y, Lam HM, Dai S, Chen Z. Crystal structures of REF6 and its complex with DNA reveal diverse recognition mechanisms. Cell Discov. 2020 Mar 31;6:17. doi: 10.1038/s41421-020-0150-6. eCollection 2020. PMID:32257379 doi:http://dx.doi.org/10.1038/s41421-020-0150-6
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