Recognition of Histone H3K4 Trimethylation by the Plant Homeodomain of PHF2 Modulates Histone Demethylation

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Feb 5

PMID 20129925

Citations 79

Authors

Hong Wen

Jingzhi Li

Tanjing Song

Ming Lu

Pu-Yeh Kan

Min Gyu Lee

Bingdong Sha

Xiaobing Shi

Affiliations

Soon will be listed here.

Abstract

Distinct lysine methylation marks on histones create dynamic signatures deciphered by the "effector" modules, although the underlying mechanisms remain unclear. We identified the plant homeodomain- and Jumonji C domain-containing protein PHF2 as a novel histone H3K9 demethylase. We show in biochemical and crystallographic analyses that PHF2 recognizes histone H3K4 trimethylation through its plant homeodomain finger and that this interaction is essential for PHF2 occupancy and H3K9 demethylation at rDNA promoters. Our study provides molecular insights into the mechanism by which distinct effector domains within a protein cooperatively modulate the "cross-talk" of histone modifications.

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References

Jenuwein T, Allis C . Translating the histone code. Science. 2001; 293(5532):1074-80. DOI: 10.1126/science.1063127. View

Shi X, Hong T, Walter K, Ewalt M, Michishita E, Hung T . ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression. Nature. 2006; 442(7098):96-9. PMC: 3089773. DOI: 10.1038/nature04835. View

Matthews A, Kuo A, Ramon-Maiques S, Han S, Champagne K, Ivanov D . RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature. 2007; 450(7172):1106-10. PMC: 2988437. DOI: 10.1038/nature06431. View

Wen H, Andrejka L, Ashton J, Karess R, Lipsick J . Epigenetic regulation of gene expression by Drosophila Myb and E2F2-RBF via the Myb-MuvB/dREAM complex. Genes Dev. 2008; 22(5):601-14. PMC: 2259030. DOI: 10.1101/gad.1626308. View

Shilatifard A . Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression. Annu Rev Biochem. 2006; 75:243-69. DOI: 10.1146/annurev.biochem.75.103004.142422. View

Shi Y . Histone lysine demethylases: emerging roles in development, physiology and disease. Nat Rev Genet. 2007; 8(11):829-33. DOI: 10.1038/nrg2218. View

Emsley P, Cowtan K . Coot: model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr. 2004; 60(Pt 12 Pt 1):2126-32. DOI: 10.1107/S0907444904019158. View

Li H, Ilin S, Wang W, Duncan E, Wysocka J, Allis C . Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF. Nature. 2006; 442(7098):91-5. PMC: 4690523. DOI: 10.1038/nature04802. View

Shi X, Kachirskaia I, Yamaguchi H, West L, Wen H, Wang E . Modulation of p53 function by SET8-mediated methylation at lysine 382. Mol Cell. 2007; 27(4):636-46. PMC: 2693209. DOI: 10.1016/j.molcel.2007.07.012. View

10.

Grandori C, Gomez-Roman N, Felton-Edkins Z, Ngouenet C, Galloway D, Eisenman R . c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I. Nat Cell Biol. 2005; 7(3):311-8. DOI: 10.1038/ncb1224. View

11.

Li B, Carey M, Workman J . The role of chromatin during transcription. Cell. 2007; 128(4):707-19. DOI: 10.1016/j.cell.2007.01.015. View

12.

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

13.

Li B, Gogol M, Carey M, Lee D, Seidel C, Workman J . Combined action of PHD and chromo domains directs the Rpd3S HDAC to transcribed chromatin. Science. 2007; 316(5827):1050-4. DOI: 10.1126/science.1139004. View

14.

Klose R, Kallin E, Zhang Y . JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet. 2006; 7(9):715-27. DOI: 10.1038/nrg1945. View

15.

Schneider T, Sheldrick G . Substructure solution with SHELXD. Acta Crystallogr D Biol Crystallogr. 2002; 58(Pt 10 Pt 2):1772-9. DOI: 10.1107/s0907444902011678. View

16.

Margueron R, Trojer P, Reinberg D . The key to development: interpreting the histone code?. Curr Opin Genet Dev. 2005; 15(2):163-76. DOI: 10.1016/j.gde.2005.01.005. View

17.

Latham J, Dent S . Cross-regulation of histone modifications. Nat Struct Mol Biol. 2007; 14(11):1017-24. DOI: 10.1038/nsmb1307. View

18.

Pena P, Davrazou F, Shi X, Walter K, Verkhusha V, Gozani O . Molecular mechanism of histone H3K4me3 recognition by plant homeodomain of ING2. Nature. 2006; 442(7098):100-3. PMC: 3190580. DOI: 10.1038/nature04814. View

19.

Agger K, Christensen J, Cloos P, Helin K . The emerging functions of histone demethylases. Curr Opin Genet Dev. 2008; 18(2):159-68. DOI: 10.1016/j.gde.2007.12.003. View

20.

Fischle W, Wang Y, Allis C . Histone and chromatin cross-talk. Curr Opin Cell Biol. 2003; 15(2):172-83. DOI: 10.1016/s0955-0674(03)00013-9. View