Multiple Mechanisms of Transcriptional Repression by YY1

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1997 Jul 1

PMID 9199306

Citations 66

Authors

K M Galvin

Y Shi

Affiliations

Soon will be listed here.

Abstract

The four C-terminal GLI-Krüppel type zinc fingers of YY1 have been identified as a transcriptional repression domain. Previous reports have proposed DNA-bending and activator-quenching mechanisms for this zinc finger-mediated repression. In addition, previous work indicated that p300 and CBP might be involved in YY1-mediated repression. We have analyzed these possible models for the zinc finger-mediated repression. The role of each zinc finger in the repression and DNA-binding functions was determined by using a structure-and-function approach. We show that zinc finger 2 of YY1 plays a central role in both DNA binding and transcriptional repression. However, a survey of a panel of YY1 mutants indicates that these two functions can be separated, which argues against the DNA-bending model for repression. We show that the physical interaction between YY1 and p300, a coactivator for CREB, is not sufficient for repression of CREB-mediated transcription. Our studies indicate that YY1 functions as an activator-specific repressor. Repression of CTF-1-directed transcription may be accomplished through direct physical interaction between YY1 and this activator. In contrast, physical interaction is not necessary for YY1 to repress Sp1- and CREB-mediated transcription. Rather, the repression likely reflects an ability of YY1 to interfere with communication between these activators and their targets within the general transcription machinery. Taken together, our results suggest that YY1 employs multiple mechanisms to achieve activator-specific repression.

Citing Articles

The Role of YY1 in the Regulation of LAG-3 Expression in CD8 T Cells and Immune Evasion in Cancer: Therapeutic Implications.

Merenstein A, Obeidat L, Zaravinos A, Bonavida B Cancers (Basel). 2025; 17(1.

PMID: 39796650 PMC: 11718991. DOI: 10.3390/cancers17010019.

YY1 knockout in pro-B cells impairs lineage commitment, enabling unusual hematopoietic lineage plasticity.

Banerjee S, Sanyal S, Hodawadekar S, Naiyer S, Bano N, Banerjee A Genes Dev. 2024; 38(17-20):887-914.

PMID: 39362773 PMC: 11535188. DOI: 10.1101/gad.351734.124.

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.

Zinc Ions Modulate YY1 Activity: Relevance in Carcinogenesis.

Figiel M, Gorka A, Gorecki A Cancers (Basel). 2023; 15(17).

PMID: 37686614 PMC: 10487186. DOI: 10.3390/cancers15174338.

The Males Absent on the First (MOF) Mediated Acetylation Alters the Protein Stability and Transcriptional Activity of YY1 in HCT116 Cells.

Wu T, Zhao B, Cai C, Chen Y, Miao Y, Chu J Int J Mol Sci. 2023; 24(10).

PMID: 37240065 PMC: 10217912. DOI: 10.3390/ijms24108719.

References

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

Eckner R, Ewen M, Newsome D, Gerdes M, DeCaprio J, Lawrence J . Molecular cloning and functional analysis of the adenovirus E1A-associated 300-kD protein (p300) reveals a protein with properties of a transcriptional adaptor. Genes Dev. 1994; 8(8):869-84. DOI: 10.1101/gad.8.8.869. View

Harlow E, Whyte P, Franza Jr B, Schley C . Association of adenovirus early-region 1A proteins with cellular polypeptides. Mol Cell Biol. 1986; 6(5):1579-89. PMC: 367684. DOI: 10.1128/mcb.6.5.1579-1589.1986. View

Luckow B, Schutz G . CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987; 15(13):5490. PMC: 305985. DOI: 10.1093/nar/15.13.5490. View

Courey A, Tjian R . Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988; 55(5):887-98. DOI: 10.1016/0092-8674(88)90144-4. View

Mermod N, ONeill E, Kelly T, Tjian R . The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989; 58(4):741-53. DOI: 10.1016/0092-8674(89)90108-6. View

Sadowski I, Ptashne M . A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989; 17(18):7539. PMC: 334849. DOI: 10.1093/nar/17.18.7539. View

Levine M, Manley J . Transcriptional repression of eukaryotic promoters. Cell. 1989; 59(3):405-8. DOI: 10.1016/0092-8674(89)90024-x. View

Pavletich N, Pabo C . Zinc finger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 A. Science. 1991; 252(5007):809-17. DOI: 10.1126/science.2028256. View

10.

Sheng M, Thompson M, Greenberg M . CREB: a Ca(2+)-regulated transcription factor phosphorylated by calmodulin-dependent kinases. Science. 1991; 252(5011):1427-30. DOI: 10.1126/science.1646483. View

11.

Seto E, Shi Y, Shenk T . YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature. 1991; 354(6350):241-5. DOI: 10.1038/354241a0. View

12.

Kaelin Jr W, Krek W, Sellers W, DeCaprio J, Ajchenbaum F, Fuchs C . Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell. 1992; 70(2):351-64. DOI: 10.1016/0092-8674(92)90108-o. View

13.

Lee T, Shi Y, Schwartz R . Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal alpha-actin transcription in embryonic myoblasts. Proc Natl Acad Sci U S A. 1992; 89(20):9814-8. PMC: 50223. DOI: 10.1073/pnas.89.20.9814. View

14.

Wang H, Rikitake Y, Carter M, Yaciuk P, Abraham S, Zerler B . Identification of specific adenovirus E1A N-terminal residues critical to the binding of cellular proteins and to the control of cell growth. J Virol. 1993; 67(1):476-88. PMC: 237385. DOI: 10.1128/JVI.67.1.476-488.1993. View

15.

Gilks C, BEAR S, Grimes H, Tsichlis P . Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to IL-2-independent growth following activation of a gene (Gfi-1) encoding a novel zinc finger protein. Mol Cell Biol. 1993; 13(3):1759-68. PMC: 359488. DOI: 10.1128/mcb.13.3.1759-1768.1993. View

16.

Lee J, Galvin K, Shi Y . Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1. Proc Natl Acad Sci U S A. 1993; 90(13):6145-9. PMC: 46884. DOI: 10.1073/pnas.90.13.6145. View

17.

Pavletich N, Pabo C . Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Science. 1993; 261(5129):1701-7. DOI: 10.1126/science.8378770. View

18.

Seto E, Lewis B, Shenk T . Interaction between transcription factors Sp1 and YY1. Nature. 1993; 365(6445):462-4. DOI: 10.1038/365462a0. View

19.

Chrivia J, Kwok R, Lamb N, Hagiwara M, Montminy M, Goodman R . Phosphorylated CREB binds specifically to the nuclear protein CBP. Nature. 1993; 365(6449):855-9. DOI: 10.1038/365855a0. View

20.

Riggs K, Saleque S, Wong K, Merrell K, Lee J, Shi Y . Yin-yang 1 activates the c-myc promoter. Mol Cell Biol. 1993; 13(12):7487-95. PMC: 364820. DOI: 10.1128/mcb.13.12.7487-7495.1993. View