| Structural highlights
Function
TYY1_HUMAN Multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes by binding to sites overlapping the transcription start site. Binds to the consensus sequence 5'-CCGCCATNTT-3'; some genes have been shown to contain a longer binding motif allowing enhanced binding; the initial CG dinucleotide can be methylated greatly reducing the binding affinity. The effect on transcription regulation is depending upon the context in which it binds and diverse mechanisms of action include direct activation or repression, indirect activation or repression via cofactor recruitment, or activation or repression by disruption of binding sites or conformational DNA changes. Its activity is regulated by transcription factors and cytoplasmic proteins that have been shown to abrogate or completely inhibit YY1-mediated activation or repression. For example, it acts as a repressor in absence of adenovirus E1A protein but as an activator in its presence. May play an important role in development and differentiation. Proposed to recruit the PRC2/EED-EZH2 complex to target genes that are transcriptional repressed. Involved in DNA repair. In vitro, binds to DNA recombination intermediate structures (Holliday junctions).[1] [2] Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair; proposed to target the INO80 complex to YY1-responsive elements.[3] [4]
Publication Abstract from PubMed
We have incorporated a bicyclic beta-turn mimetic (BTD; beta-turn dipeptide) into a zinc finger, creating a zinc finger with an artificial beta-turn. The designed peptide chelates zinc and has the same fold as the unmodified native zinc finger (finger 3 of the human YY1 protein). A combination of 1H NMR and structure calculations reveals that, in solution, this zinc finger has a fold similar to the known wild-type crystal structure and to other zinc fingers containing the consensus sequence X3-Cys-X4-Cys-X12-His-X3-His-X. The peptide was designed with BTD between the chelating cysteine residues, with BTD forming a type II' beta-turn linking the two strands of a distorted anti-parallel beta-sheet. The C-terminal portion of the peptide forms a helix with zinc co-ordinating histidine residues on successive turns of the helix. This work represents a step towards developing methods by which parts of a target protein may be replaced by peptide mimetics.
Design, synthesis and structure of a zinc finger with an artificial beta-turn.,Viles JH, Patel SU, Mitchell JB, Moody CM, Justice DE, Uppenbrink J, Doyle PM, Harris CJ, Sadler PJ, Thornton JM J Mol Biol. 1998 Jun 19;279(4):973-86. PMID:9642075[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cai Y, Jin J, Yao T, Gottschalk AJ, Swanson SK, Wu S, Shi Y, Washburn MP, Florens L, Conaway RC, Conaway JW. YY1 functions with INO80 to activate transcription. Nat Struct Mol Biol. 2007 Sep;14(9):872-4. Epub 2007 Aug 26. PMID:17721549 doi:http://dx.doi.org/nsmb1276
- ↑ Wu S, Shi Y, Mulligan P, Gay F, Landry J, Liu H, Lu J, Qi HH, Wang W, Nickoloff JA, Wu C, Shi Y. A YY1-INO80 complex regulates genomic stability through homologous recombination-based repair. Nat Struct Mol Biol. 2007 Dec;14(12):1165-72. Epub 2007 Nov 18. PMID:18026119 doi:http://dx.doi.org/10.1038/nsmb1332
- ↑ Cai Y, Jin J, Yao T, Gottschalk AJ, Swanson SK, Wu S, Shi Y, Washburn MP, Florens L, Conaway RC, Conaway JW. YY1 functions with INO80 to activate transcription. Nat Struct Mol Biol. 2007 Sep;14(9):872-4. Epub 2007 Aug 26. PMID:17721549 doi:http://dx.doi.org/nsmb1276
- ↑ Wu S, Shi Y, Mulligan P, Gay F, Landry J, Liu H, Lu J, Qi HH, Wang W, Nickoloff JA, Wu C, Shi Y. A YY1-INO80 complex regulates genomic stability through homologous recombination-based repair. Nat Struct Mol Biol. 2007 Dec;14(12):1165-72. Epub 2007 Nov 18. PMID:18026119 doi:http://dx.doi.org/10.1038/nsmb1332
- ↑ Viles JH, Patel SU, Mitchell JB, Moody CM, Justice DE, Uppenbrink J, Doyle PM, Harris CJ, Sadler PJ, Thornton JM. Design, synthesis and structure of a zinc finger with an artificial beta-turn. J Mol Biol. 1998 Jun 19;279(4):973-86. PMID:9642075 doi:http://dx.doi.org/S0022-2836(98)91764-8
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