CXXC Finger Protein 1 Restricts the Setd1A Histone H3K4 Methyltransferase Complex to Euchromatin

Overview

Journal FEBS J

Specialty Biochemistry

Date 2009 Dec 3

PMID 19951360

Citations 34

Authors

Courtney M Tate

Jeong-Heon Lee

David G Skalnik

Affiliations

Soon will be listed here.

Abstract

CXXC finger protein 1 (Cfp1), encoded by the CXXC1 gene, is a component of the euchromatic Setd1A histone H3K4 methyltransferase complex, and is a critical regulator of histone methylation, cytosine methylation, cellular differentiation, and vertebrate development. Murine embryonic stem (ES) cells lacking Cfp1 (CXXC1(-/-)) are viable but show increased levels of global histone H3K4 methylation, suggesting that Cfp1 functions to inhibit or restrict the activity of the Setd1A histone H3K4 methyltransferase complex. The studies reported here reveal that ES cells lacking Cfp1 contain decreased levels of Setd1A and show subnuclear mislocalization of both Setd1A and trimethylation of histone H3K4 with regions of heterochromatin. Remarkably, structure-function studies reveal that expression of either the N-terminal fragment of Cfp1 (amino acids 1-367) or the C-terminal fragment of Cfp1 (amino acids 361-656) is sufficient to restore appropriate levels of Setd1A in CXXC1(-/-) ES cells. Furthermore, functional analysis of various Cfp1 point mutations reveals that retention of either Cfp1 DNA-binding activity or association with the Setd1 histone H3K4 methyltransferase complex is required to restore normal Setd1A levels. In contrast, expression of full-length Cfp1 in CXXC1(-/-) ES cells is required to restrict Setd1A and histone H3K4 trimethylation to euchromatin, indicating that both Cfp1 DNA-binding activity and interaction with the Setd1A complex are required for appropriate genomic targeting of the Setd1A complex. These studies illustrate the complexity of Cfp1 function, and identify Cfp1 as a regulator of Setd1A genomic targeting.

Citing Articles

Cfp1 Controls Cardiomyocyte Maturation by Modifying Histone H3K4me3 of Structural, Metabolic, and Contractile Related Genes.

Li C, Zhang Y, Shen J, Bao H, Zhao Y, Li D Adv Sci (Weinh). 2024; 11(11):e2305992.

PMID: 38196272 PMC: 10953565. DOI: 10.1002/advs.202305992.

Deep thermal profiling for detection of functional proteoform groups.

Kurzawa N, Leo I, Stahl M, Kunold E, Becher I, Audrey A Nat Chem Biol. 2023; 19(8):962-971.

PMID: 36941476 PMC: 10374440. DOI: 10.1038/s41589-023-01284-8.

Identification of a novel target of SETD1A histone methyltransferase and the clinical significance in pancreatic cancer.

Ishii T, Akiyama Y, Shimada S, Kabashima A, Asano D, Watanabe S Cancer Sci. 2022; 114(2):463-476.

PMID: 36271761 PMC: 9899616. DOI: 10.1111/cas.15615.

Schizophrenia-associated differential DNA methylation in brain is distributed across the genome and annotated to MAD1L1, a locus at which DNA methylation and transcription phenotypes share genetic variation with schizophrenia risk.

McKinney B, McClain L, Hensler C, Wei Y, Klei L, Lewis D Transl Psychiatry. 2022; 12(1):340.

PMID: 35987687 PMC: 9392724. DOI: 10.1038/s41398-022-02071-0.

CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription.

Yang L, Hu H, Han Y, Tang Z, Gao J, Zhou Q Cancer Gene Ther. 2022; 29(12):1895-1907.

PMID: 35864225 PMC: 9750859. DOI: 10.1038/s41417-022-00503-z.

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

McKinnell I, Ishibashi J, Le Grand F, Punch V, Addicks G, Greenblatt J . Pax7 activates myogenic genes by recruitment of a histone methyltransferase complex. Nat Cell Biol. 2007; 10(1):77-84. PMC: 2739814. DOI: 10.1038/ncb1671. View

Ng H, Robert F, Young R, Struhl K . Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Mol Cell. 2003; 11(3):709-19. DOI: 10.1016/s1097-2765(03)00092-3. View

Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva F, Li M . SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004; 6(8):731-40. DOI: 10.1038/ncb1151. View

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

Noma K , Allis C, Grewal S . Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science. 2001; 293(5532):1150-5. DOI: 10.1126/science.1064150. View

Wysocka J, Myers M, Laherty C, Eisenman R, Herr W . Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes Dev. 2003; 17(7):896-911. PMC: 196026. DOI: 10.1101/gad.252103. View

Domer P, Fakharzadeh S, Chen C, Jockel J, Johansen L, Silverman G . Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product. Proc Natl Acad Sci U S A. 1993; 90(16):7884-8. PMC: 47247. DOI: 10.1073/pnas.90.16.7884. View

Boggs B, Cheung P, Heard E, Spector D, Craig Chinault A, Allis C . Differentially methylated forms of histone H3 show unique association patterns with inactive human X chromosomes. Nat Genet. 2001; 30(1):73-6. DOI: 10.1038/ng787. View

10.

Prasad R, Yano T, Sorio C, Nakamura T, Rallapalli R, Gu Y . Domains with transcriptional regulatory activity within the ALL1 and AF4 proteins involved in acute leukemia. Proc Natl Acad Sci U S A. 1995; 92(26):12160-4. PMC: 40316. DOI: 10.1073/pnas.92.26.12160. View

11.

Couture J, Collazo E, Trievel R . Molecular recognition of histone H3 by the WD40 protein WDR5. Nat Struct Mol Biol. 2006; 13(8):698-703. DOI: 10.1038/nsmb1116. 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.

Ma Q, Alder H, Nelson K, Chatterjee D, Gu Y, Nakamura T . Analysis of the murine All-1 gene reveals conserved domains with human ALL-1 and identifies a motif shared with DNA methyltransferases. Proc Natl Acad Sci U S A. 1993; 90(13):6350-4. PMC: 46926. DOI: 10.1073/pnas.90.13.6350. View

14.

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

15.

Yu B, Hess J, Horning S, Brown G, Korsmeyer S . Altered Hox expression and segmental identity in Mll-mutant mice. Nature. 1995; 378(6556):505-8. DOI: 10.1038/378505a0. View

16.

Milne T, Dou Y, Martin M, Brock H, Roeder R, Hess J . MLL associates specifically with a subset of transcriptionally active target genes. Proc Natl Acad Sci U S A. 2005; 102(41):14765-70. PMC: 1253553. DOI: 10.1073/pnas.0503630102. View

17.

Gregory G, Vakoc C, Rozovskaia T, Zheng X, Patel S, Nakamura T . Mammalian ASH1L is a histone methyltransferase that occupies the transcribed region of active genes. Mol Cell Biol. 2007; 27(24):8466-79. PMC: 2169421. DOI: 10.1128/MCB.00993-07. View

18.

Tkachuk D, Kohler S, Cleary M . Involvement of a homolog of Drosophila trithorax by 11q23 chromosomal translocations in acute leukemias. Cell. 1992; 71(4):691-700. DOI: 10.1016/0092-8674(92)90602-9. View

19.

Carlone D, Hart S, Ladd P, Skalnik D . Cloning and characterization of the gene encoding the mouse homologue of CpG binding protein. Gene. 2002; 295(1):71-7. DOI: 10.1016/s0378-1119(02)00820-x. View

20.

Lee J, Skalnik D . CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex. J Biol Chem. 2005; 280(50):41725-31. DOI: 10.1074/jbc.M508312200. View