Mi2β Is Required for γ-Globin Gene Silencing: Temporal Assembly of a GATA-1-FOG-1-Mi2 Repressor Complex in β-YAC Transgenic Mice

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Activation of γ-globin gene expression in adults is known to be therapeutic for sickle cell disease. Thus, it follows that the converse, alleviation of repression, would be equally effective, since the net result would be the same: an increase in fetal hemoglobin. A GATA-1-FOG-1-Mi2 repressor complex was recently demonstrated to be recruited to the −566 GATA motif of the ^Aγ-globin gene. We show that Mi2β is essential for γ-globin gene silencing using Mi2β conditional knockout β-YAC transgenic mice. In addition, increased expression of ^Aγ-globin was detected in adult blood from β-YAC transgenic mice containing a T>G HPFH point mutation at the −566 GATA silencer site. ChIP experiments demonstrated that GATA-1 is recruited to this silencer at day E16, followed by recruitment of FOG-1 and Mi2 at day E17 in wild-type β-YAC transgenic mice. Recruitment of the GATA-1–mediated repressor complex was disrupted by the −566 HPFH mutation at developmental stages when it normally binds. Our data suggest that a temporal repression mechanism is operative in the silencing of γ-globin gene expression and that either a trans-acting Mi2β knockout deletion mutation or the cis-acting −566 ^Aγ-globin HPFH point mutation disrupts establishment of repression, resulting in continued γ-globin gene transcription during adult definitive erythropoiesis.

Vyšlo v časopise: Mi2β Is Required for γ-Globin Gene Silencing: Temporal Assembly of a GATA-1-FOG-1-Mi2 Repressor Complex in β-YAC Transgenic Mice. PLoS Genet 8(12): e32767. doi:10.1371/journal.pgen.1003155
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003155

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Zdroje

1. Harju-BakerS, CostaFC, FedosyukH, NeadesR, PetersonKR (2008) Silencing of Aγ-globin gene expression during adult definitive erythropoiesis mediated by GATA-1-FOG-1-Mi2 complex binding at the −566 GATA site. Mol Cell Biol 28: 3101–3113.

2. ChenZ, LuoHY, BasranRK, HsuTH, MangDW, et al. (2008) A T-to-G transversion at nucleotide −567 upstream of HBG2 in a GATA-1 binding motif is associated with elevated hemoglobin F. Mol Cell Biol 28: 4386–4393.

3. OhnedaK, YamamotoM (2002) Roles of hematopoietic transcription factors GATA-1 and GATA-2 in the development of red blood cell lineage. Acta Haematol 108: 237–245.

4. SpiegelmanBM, HeinrichR (2004) Biological control through regulated transcriptional coactivators. Cell 119: 157–167.

5. HongW, NakazawaM, ChenYY, KoriR, VakocCR, RakowskiC, BlobelGA (2005) FOG-1 recruits the NuRD repressor complex to mediate transcriptional repression by GATA-1. EMBO J 24: 2367–2378.

6. RodriguezP, BonteE, KrijgsveldJ, KolodjiezKE, GuyotB, et al. (2005) GATA-1 forms distinct activating and repressive complexes in erythroid cells. EMBO J 24: 2354–2366.

7. CrispinoJD, LodishMB, MacKayJP, OrkinSH (1997) Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: the GATA-1:FOG complex. Mol Cell 3: 219–228.

8. KimSI, BultmanSJ, JingH, BlobelGA, BresnickEH (2007) Dissecting molecular steps in chromatin domain activation during hematopoietic differentiation. Mol Cell Biol 27: 4551–4565.

9. MiccioA, WangY, HongW, GregoryGD, WangH, et al. (2010) NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development. EMBO J 29: 442–456.

10. MiccioA, BlobelGA (2010) Role of the GATA-1/FOG-1/NuRD pathway in the expression of human beta-like globin genes. Mol Cell Biol 30: 3460–3470.

11. BowenNJ, FujitaN, KajitaM, WadePA (2004) Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677: 52–57.

12. DenslowSA, WadePA (2007) The human Mi-2/NuRD complex and gene regulation. Oncogene 26: 5433–5438.

13. WilliamsCJ, NaitoT, ArcoPG, SeavittJR, CashmanSM, et al. (2004) The chromatin remodeler Mi-2beta is required for CD4 expression and T cell development. Immunity 20: 19–33.

14. PetersonKR, FedosyukH, ZelenchukL, NakamotoB, YannakiE, et al. (2004) Transgenic Cre expression mice for generation of erythroid-specific gene alterations. Genesis 39: 1–9.

15. PetersonKR, ZitnikG, HuxleyC, LowreyCH, GnirkeA, et al. (1993) Use of yeast artificial chromosomes (YACs) for studying control of gene expression: correct regulation of the genes of a human beta-globin locus YAC following transfer to mouse erythroleukemia cell lines. Proc Natl Acad Sci USA 90: 11207–11211.

16. BlauCA, BarbasCFIII, BomhoffA, NeadesRY, YanJ, et al. (2005) γ-globin gene expression in CID-dependent multi-potential cells established from β-YAC transgenic mice. J Biol Chem 280: 36642–36647.

17. WeissMJ, KellerG, OrkinSH (1994) Novel insights into erythroid development revealed through in vitro differentiation of GATA-1 embryonic stem cells. Genes Dev 8: 1184–1197.

18. BresnickEH, LeeHY, FujiwaraT, JohnsonKD, KelesS (2010) GATA switches as developmental drivers. J Biol Chem 285: 31087–31093.

19. GrassJA, BoyerME, PalS, WuJ, WeissMJ, et al. (2003) GATA-1-dependent transcriptional repression of GATA-2 via disruption of positive autoregulation and domain-wide chromatin remodeling. Proc Natl Acad Sci USA 15: 8811–8816.

20. PalS, CantorAB, JohnsonKD, MoranTB, BoyerME, et al. (2004) Coregulator-dependent facilitation of chromatin occupancy by GATA-1. Proc Natl Acad Sci USA 4: 980–985.

21. PetersonKR, LiQ, CleggCH, FurukawaT, NavasPA, et al. (1995) Use of YACs in studies of mammalian development: Production of β-globin locus YAC mice carrying human globin developmental mutants. Proc Natl Acad Sci USA 92: 5655–5659.

22. BerryM, GrosveldF, DillonN (1992) A single point mutation is the cause of the Greek form of hereditary persistence of fetal haemoglobin. Nature 358: 499–502.

23. TheinSL, MenzelS, LathropM, GarnerC (2009) Control of fetal hemoglobin: new insights emerging from genomics and clinical implications. Hum Mol Genet 18: 216–223.

24. TheinSL, CraigJE (1998) Genetics of Hb F/F cell variance in adults and heterocellular hereditary persistence of fetal hemoglobin. Hemoglobin 22: 410–414.

25. SankaranVG, MenneTF, XuJ, AkieTE, LettreG, et al. (2008) Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science 322: 1839–1842.

26. LopezRA, SchoetzS, DeAngelisK, O'NeillD, BankA (2002) Multiple hematopoietic defects and delayed globin switching in Ikaros null mice. Proc Natl Acad Sci USA 99: 602–607.

27. StamatoyannopoulosG (2005) Control of globin gene expression during development and erythroid differentiation. Exp Hematol 33: 259–271.

28. TanabeO, McPheeD, KobayashiS, ShenY, BrandtW, et al. (2007) Embryonic and fetal β-globin gene repression by the orphan nuclear receptors, TR2 and TR4. EMBO J 26: 2295–2306.

29. BottardiS, RossJ, BourgoinV, Fotouhi-ArdakaniN, Affar elB, et al. (2009) Ikaros and GATA-1 combinatorial effect is required for silencing of human γ-globin genes. Mol Cell Biol 29: 1526–1537.

30. GnanapragasamMN, ScarsdaleJN, AmayaML, WebbHD, DesaiMA, et al. (2011) p66 α-MBD2 coiled-coil interaction and recruitment of Mi2 are critical for globin gene silencing by the MBD2-NuRD complex. Proc Natl Acad Sci USA 108: 7487–7492.

31. HarjuS, NavasPA, StamatoyannopoulosG, PetersonKR (2005) Genome architecture of the human beta-globin locus affects developmental regulation of gene expression. Mol Cell Biol 25: 8765–8778.

32. LarionovA, KrauseA, MillerW (2005) A standard curve based method for relative real time PCR data processing. BMC Bioinform 6: 62.

33. PfafflMW (2001) A new mathematical model for relative quantification in real-time PCR. Nucleic Acids Res 29: e45.

34. NavasPA, PetersonKR, LiQ, SkarpidiE, RodheA, et al. (1998) Developmental specificity of the interaction between the locus control region and embryonic or fetal globin genes in transgenic mice with an HS3 core deletion. Mol Cell Biol 18: 4188–4196.

35. BallesterM, CastelloA, IbanezE, SanchezA, FolchJM (2004) Real-time quantitative PCR-based system for determining transgene copy number in transgenic animals. Biotechniques 37: 610–613.

36. NavasPA, PetersonKR, LiQ, McArthurM, StamatoyannopoulosG (2001) The 5′HS4 core element of the human beta-globin locus control region is required for high-level globin gene expression in definitive but not in primitive erythropoiesis. J Mol Biol 312: 17–26.

37. KashiwagiM, MorganBA, GeorgopoulosK (2007) The chromatin remodeler Mi-2beta is required for establishment of the basal epidermis and normal differentiation of its progeny. Development 134: 1571–1582.

38. ZengPY, VakocCR, ChenZC, BlobelGA, BergerSL (2006) In vivo dual cross-linking for identification of indirect DNA-associated proteins by chromatin immunoprecipitation. Biotechniques 41: 696–698.

39. LivakKJ, SchmittgenTD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25: 402–408.

40. GiardineB, BorgJ, HiggsDR, PetersonKR, PhilipsenS, et al. (2010) Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach. Nature Genet 43: 295–301.

41. AmoyalI, FibachE (2004) Flow cytometric analysis of fetal hemoglobin in erythroid precursors of beta-thalassemia. Clin Lab Haematol 26: 187–193.

42. BohmerRM (2001) Flow cytometry of erythroid cells in culture: bivariate profiles of fetal and adult hemoglobins. Meth Cell Biol 64: 139–152.

43. SheltonJB, SheltonJR, SchroederWA (1984) High performance liquid chromatographic separation of globins on a large-pore C4 column. J Liquid Chromatogr 7: 1969–1997.