PcG Recruitment by the YY1 REPO Domain Can Be Mediated by Yaf2

Overview

Journal J Cell Biochem

Specialties Biochemistry
Cell Biology

Date 2009 Dec 5

PMID 19960508

Citations 25

Authors

Frank Wilkinson

Heather Pratt

Michael L Atchison

Affiliations

Soon will be listed here.

Abstract

The Polycomb Group (PcG) complex of transcriptional repressors is critical for the maintenance of stage-specific developmental gene expression, stem cell maintenance and for large-scale chromosomal dynamics. Functional deficiency of a single PcG gene can severely compromise PcG function, leading to developmental defects, embryonic lethality, or a number of malignancies. Despite the critical nature of PcG proteins, the mechanisms by which these complexes mediate their effects are relatively uncharacterized. Nearly all vertebrate PcG proteins lack inherent DNA binding capacity, making it unclear how they are targeted to Polycomb response element (PRE) sequences. Transcription factor YY1 is a functional ortholog of a Drosophila PcG protein, Pleiohomeotic (PHO), one of the few PcG proteins with specific DNA binding capability, and YY1 can recruit PcG proteins to specific DNA sequences. A small 25 amino acid YY1 domain (the REPO domain) is necessary and sufficient for recruitment of PcG proteins to DNA and for transcriptional repression. We show here that the YY1 REPO domain interacts with PcG protein Yaf2 and recruits Yaf2 to DNA. Interaction is lost when the YY1 REPO domain is deleted. In addition we show that Yaf2, when linked to a heterologous DNA binding domain, can recruit PcG proteins to DNA leading to transcriptional repression. When the Drosophila homolog of Yaf2 (dRYBP) is mutated, PcG recruitment to DNA is reduced. Taken together, our results suggest that Yaf2 serves as a molecular bridge between YY1 and other PcG complex proteins.

Citing Articles

Impact of chromatin on HIV-1 latency: a multi-dimensional perspective.

Jones J, Gunderson C, Wigdahl B, Nonnemacher M Epigenetics Chromatin. 2025; 18(1):9.

PMID: 40055755 PMC: 11889793. DOI: 10.1186/s13072-025-00573-x.

Yin Yang 1: Function, Mechanisms, and Glia.

Rodriguez-Campuzano A, Castelan F, Hernandez-Kelly L, Felder-Schmittbuhl M, Ortega A Neurochem Res. 2025; 50(2):96.

PMID: 39904836 PMC: 11794380. DOI: 10.1007/s11064-025-04345-7.

Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1.

Donald H, Blane A, Buthelezi S, Naicker P, Stoychev S, Majakwara J Biosci Rep. 2023; 43(10).

PMID: 37815922 PMC: 10611921. DOI: 10.1042/BSR20231295.

The Role of Polycomb Group Protein BMI1 in DNA Repair and Genomic Stability.

Fitieh A, Locke A, Motamedi M, Ismail I Int J Mol Sci. 2021; 22(6).

PMID: 33804165 PMC: 7998361. DOI: 10.3390/ijms22062976.

Roles Played by YY1 in Embryonic, Adult and Cancer Stem Cells.

Martinez-Ruiz G, Morales-Sanchez A, Pacheco-Hernandez A Stem Cell Rev Rep. 2021; 17(5):1590-1606.

PMID: 33728560 PMC: 8553684. DOI: 10.1007/s12015-021-10151-9.

References

Ringrose L, Rehmsmeier M, Dura J, Paro R . Genome-wide prediction of Polycomb/Trithorax response elements in Drosophila melanogaster. Dev Cell. 2003; 5(5):759-71. DOI: 10.1016/s1534-5807(03)00337-x. View

Kim H, Kang K, Kim J . AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. Nucleic Acids Res. 2009; 37(9):2940-50. PMC: 2685092. DOI: 10.1093/nar/gkp149. View

Mahmoudi T, Zuijderduijn L, Mohd-Sarip A, Verrijzer C . GAGA facilitates binding of Pleiohomeotic to a chromatinized Polycomb response element. Nucleic Acids Res. 2003; 31(14):4147-56. PMC: 167640. DOI: 10.1093/nar/gkg479. View

Gorfinkiel N, Fanti L, Melgar T, Garcia E, Pimpinelli S, Guerrero I . The Drosophila Polycomb group gene Sex combs extra encodes the ortholog of mammalian Ring1 proteins. Mech Dev. 2004; 121(5):449-62. DOI: 10.1016/j.mod.2004.03.019. View

Mihaly J, Mishra R, Karch F . A conserved sequence motif in Polycomb-response elements. Mol Cell. 1998; 1(7):1065-6. DOI: 10.1016/s1097-2765(00)80107-0. View

Satijn D, Hamer K, den Blaauwen J, Otte A . The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos. Mol Cell Biol. 2001; 21(4):1360-9. PMC: 99588. DOI: 10.1128/MCB.21.4.1360-1369.2001. View

Mohd-Sarip A, Venturini F, Chalkley G, Verrijzer C . Pleiohomeotic can link polycomb to DNA and mediate transcriptional repression. Mol Cell Biol. 2002; 22(21):7473-83. PMC: 135681. DOI: 10.1128/MCB.22.21.7473-7483.2002. View

Kalenik J, Chen D, Bradley M, Chen S, Lee T . Yeast two-hybrid cloning of a novel zinc finger protein that interacts with the multifunctional transcription factor YY1. Nucleic Acids Res. 1997; 25(4):843-9. PMC: 146511. DOI: 10.1093/nar/25.4.843. View

Blastyak A, Mishra R, Karch F, Gyurkovics H . Efficient and specific targeting of Polycomb group proteins requires cooperative interaction between Grainyhead and Pleiohomeotic. Mol Cell Biol. 2006; 26(4):1434-44. PMC: 1367177. DOI: 10.1128/MCB.26.4.1434-1444.2006. View

10.

Kirmizis A, Bartley S, Kuzmichev A, Margueron R, Reinberg D, Green R . Silencing of human polycomb target genes is associated with methylation of histone H3 Lys 27. Genes Dev. 2004; 18(13):1592-605. PMC: 443521. DOI: 10.1101/gad.1200204. View

11.

Garcia E, del Mar Lorente M, Moreno J, Vidal M . RYBP, a new repressor protein that interacts with components of the mammalian Polycomb complex, and with the transcription factor YY1. EMBO J. 1999; 18(12):3404-18. PMC: 1171420. DOI: 10.1093/emboj/18.12.3404. View

12.

Shimell M, Peterson A, Burr J, Simon J, OConnor M . Functional analysis of repressor binding sites in the iab-2 regulatory region of the abdominal-A homeotic gene. Dev Biol. 2000; 218(1):38-52. DOI: 10.1006/dbio.1999.9576. View

13.

Valk-Lingbeek M, Bruggeman S, van Lohuizen M . Stem cells and cancer; the polycomb connection. Cell. 2004; 118(4):409-18. DOI: 10.1016/j.cell.2004.08.005. View

14.

Bejarano F, Gonzalez I, Vidal M, Busturia A . The Drosophila RYBP gene functions as a Polycomb-dependent transcriptional repressor. Mech Dev. 2005; 122(10):1118-29. DOI: 10.1016/j.mod.2005.06.001. View

15.

Brown J, Mucci D, Whiteley M, Dirksen M, Kassis J . The Drosophila Polycomb group gene pleiohomeotic encodes a DNA binding protein with homology to the transcription factor YY1. Mol Cell. 1998; 1(7):1057-64. DOI: 10.1016/s1097-2765(00)80106-9. View

16.

Lund A, van Lohuizen M . Polycomb complexes and silencing mechanisms. Curr Opin Cell Biol. 2004; 16(3):239-46. DOI: 10.1016/j.ceb.2004.03.010. View

17.

Atchison L, Ghias A, Wilkinson F, Bonini N, Atchison M . Transcription factor YY1 functions as a PcG protein in vivo. EMBO J. 2003; 22(6):1347-58. PMC: 151054. DOI: 10.1093/emboj/cdg124. View

18.

Satijn D, Gunster M, van der Vlag J, Hamer K, Schul W, Alkema M . RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor. Mol Cell Biol. 1997; 17(7):4105-13. PMC: 232264. DOI: 10.1128/MCB.17.7.4105. View

19.

Levine S, King I, Kingston R . Division of labor in polycomb group repression. Trends Biochem Sci. 2004; 29(9):478-85. DOI: 10.1016/j.tibs.2004.07.007. View

20.

Ringrose L, Paro R . Polycomb/Trithorax response elements and epigenetic memory of cell identity. Development. 2006; 134(2):223-32. DOI: 10.1242/dev.02723. View