CXXC Finger Protein 1 Contains Redundant Functional Domains That Support Embryonic Stem Cell Cytosine Methylation, Histone Methylation, and Differentiation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2009 May 13

PMID 19433449

Citations 19

Authors

Courtney M Tate

Jeong-Heon Lee

David G Skalnik

Affiliations

Soon will be listed here.

Abstract

CXXC finger protein 1 (Cfp1) is a regulator of both cytosine methylation and histone methylation. Murine embryonic stem (ES) cells lacking Cfp1 exhibit a decreased plating efficiency, decreased cytosine methylation, elevated global levels of histone H3-Lys4 trimethylation, and a failure to differentiate in vitro. Remarkably, transfection studies reveal that expression of either the amino half of Cfp1 (amino acids 1 to 367 [Cfp1(1-367)]) or the carboxyl half of Cfp1 (Cfp1(361-656)) is sufficient to correct all of the defects observed with ES cells that lack Cfp1. However, a point mutation (C169A) that abolishes DNA-binding activity of Cfp1 ablates the rescue activity of the Cfp1(1-367) fragment, and a point mutation (C375A) that abolishes the interaction of Cfp1 with the Setd1 histone H3-Lys4 methyltransferase complexes ablates the rescue activity of the Cfp1(361-656) fragment. Introduction of both the C169A and C375A point mutations ablates the rescue activity of the full-length Cfp1 protein. These results indicate that retention of either the Cfp1 DNA-binding domain or Setd1 interaction domain is required for Cfp1 rescue activity, and they illustrate the functional complexity of this critical epigenetic regulator. A model is presented for how epigenetic cross talk may explain the finding of redundant functional domains within Cfp1.

Citing Articles

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References

Halbach T, Scheer N, Werr W . Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins. Nucleic Acids Res. 2000; 28(18):3542-50. PMC: 110726. DOI: 10.1093/nar/28.18.3542. View

Terranova R, Agherbi H, Boned A, Meresse S, Djabali M . Histone and DNA methylation defects at Hox genes in mice expressing a SET domain-truncated form of Mll. Proc Natl Acad Sci U S A. 2006; 103(17):6629-34. PMC: 1440589. DOI: 10.1073/pnas.0507425103. View

Rasmussen T . Embryonic stem cell differentiation: a chromatin perspective. Reprod Biol Endocrinol. 2003; 1:100. PMC: 293417. DOI: 10.1186/1477-7827-1-100. View

Ruthenburg A, Li H, Patel D, Allis C . Multivalent engagement of chromatin modifications by linked binding modules. Nat Rev Mol Cell Biol. 2007; 8(12):983-94. PMC: 4690530. DOI: 10.1038/nrm2298. 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

Pradhan M, Esteve P, Chin H, Samaranayke M, Kim G, Pradhan S . CXXC domain of human DNMT1 is essential for enzymatic activity. Biochemistry. 2008; 47(38):10000-9. DOI: 10.1021/bi8011725. View

Pesce M, Scholer H . Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells. 2001; 19(4):271-8. DOI: 10.1634/stemcells.19-4-271. View

Paulsen M, Ferguson-Smith A . DNA methylation in genomic imprinting, development, and disease. J Pathol. 2001; 195(1):97-110. DOI: 10.1002/path.890. View

Shi X, Kachirskaia I, Walter K, Kuo J, Lake A, Davrazou F . Proteome-wide analysis in Saccharomyces cerevisiae identifies several PHD fingers as novel direct and selective binding modules of histone H3 methylated at either lysine 4 or lysine 36. J Biol Chem. 2006; 282(4):2450-5. PMC: 2735445. DOI: 10.1074/jbc.C600286200. View

10.

Ono R, Taki T, Taketani T, Taniwaki M, Kobayashi H, Hayashi Y . LCX, leukemia-associated protein with a CXXC domain, is fused to MLL in acute myeloid leukemia with trilineage dysplasia having t(10;11)(q22;q23). Cancer Res. 2002; 62(14):4075-80. View

11.

Puech A, Dupressoir A, Loireau M, Mattei M, Heidmann T . Characterization of two age-induced intracisternal A-particle-related transcripts in the mouse liver. Transcriptional read-through into an open reading frame with similarities to the yeast ccr4 transcription factor. J Biol Chem. 1997; 272(9):5995-6003. DOI: 10.1074/jbc.272.9.5995. View

12.

Peterson C, Laniel M . Histones and histone modifications. Curr Biol. 2004; 14(14):R546-51. DOI: 10.1016/j.cub.2004.07.007. View

13.

Schindler U, Beckmann H, Cashmore A . HAT3.1, a novel Arabidopsis homeodomain protein containing a conserved cysteine-rich region. Plant J. 1993; 4(1):137-50. DOI: 10.1046/j.1365-313x.1993.04010137.x. View

14.

Tsukada Y, Fang J, Erdjument-Bromage H, Warren M, Borchers C, Tempst P . Histone demethylation by a family of JmjC domain-containing proteins. Nature. 2005; 439(7078):811-6. DOI: 10.1038/nature04433. View

15.

Caiafa P, Zampieri M . DNA methylation and chromatin structure: the puzzling CpG islands. J Cell Biochem. 2004; 94(2):257-65. DOI: 10.1002/jcb.20325. View

16.

Li E . Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002; 3(9):662-73. DOI: 10.1038/nrg887. View

17.

Balaghi M, Wagner C . DNA methylation in folate deficiency: use of CpG methylase. Biochem Biophys Res Commun. 1993; 193(3):1184-90. DOI: 10.1006/bbrc.1993.1750. View

18.

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

19.

Li E, Bestor T, Jaenisch R . Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell. 1992; 69(6):915-26. DOI: 10.1016/0092-8674(92)90611-f. View

20.

Keller G, Kennedy M, Papayannopoulou T, Wiles M . Hematopoietic commitment during embryonic stem cell differentiation in culture. Mol Cell Biol. 1993; 13(1):473-86. PMC: 358927. DOI: 10.1128/mcb.13.1.473-486.1993. View