Disease relevance of YY1

• Because YY1 also down-regulates promoter activities of CXCR4, another major coreceptor for HIV-1 and HIV-1 long terminal repeat, this transcription factor may play a critical role in the pathogenesis of HIV-1 disease [1].
• Moreover, we demonstrated the interaction between endogenous AP-2 and YY1 factors in the BT-474 mammary adenocarcinoma cell line [2].
• In addition, inhibition of endogenous YY1 protein by an antisense decreased the transcription of an AP-2-responsive ERBB2 reporter plasmid in BT-474 breast cancer cells [2].
• Finally, we have found that overexpression of the adenovirus E1A protein represses expression of a reporter gene directed by the YY1 promoter [3].
• Hepatitis C virus core protein recruits nucleolar phosphoprotein B23 and coactivator p300 to relieve the repression effect of transcriptional factor YY1 on B23 gene expression [4].

Psychiatry related information on YY1

• A deletion in MDR1 (Delta amino acids 78-97), which alters the substrate stimulation of its ATPase activity, similarly alters the drug dependence of nucleotide trapping [5].
• Using a cross-sectional survey design, 2,297 adolescents who attended public schools in grades 7 through 12 in one isolated rural Mississippi River Delta county were assessed via a standardized health behavior survey [6].

High impact information on YY1

• Conversely, YY1 overexpression stimulates p53 ubiquitination and degradation [7].
• We show that an element within D4Z4 specifically binds a multiprotein complex consisting of YY1, a known transcriptional repressor, HMGB2, an architectural protein, and nucleolin [8].
• We propose that, under appropriate conditions, YY1 can function like TBP, as a factor that binds to the core promoter and recruits the polymerase to the initiation complex [9].
• delta F508 is the most frequent cystic fibrosis (CF) mutation and accounts for approximately 70% of CF chromosomes worldwide [10].
• TATA-binding protein-independent initiation: YY1, TFIIB, and RNA polymerase II direct basal transcription on supercoiled template DNA [9].

Chemical compound and disease context of YY1

• Introduction of exogenous Brm to these cells suppressed recruitment of protein complexes containing YY1 and histone deacetylase (HDAC) 1 and 2 to the 5'-long terminal repeat region of the integrated provirus, leading to the enhancement of acetylation of specific lysine residues in histone H4 located in this region [11].
• Chloride conductance and genetic background modulate the cystic fibrosis phenotype of Delta F508 homozygous twins and siblings [12].
• The most common defect in cystic fibrosis, deletion of phenylalanine from position 508 of the cystic fibrosis transmembrane conductance regulator (Delta F508 CFTR), decreases the trafficking of this protein to the cell surface membrane [13].
• The Delta 32 mutation of the chemokine-receptor 5 gene neither is correlated with chronic hepatitis C nor does it predict response to therapy with interferon-alpha and ribavirin [14].
• Strain F62 (Opa-Pil+), expressing the lacto-N-neotetraose and the galNac-lacto-N-neotetraose LOS, and its isogenic derivative that expressed only the lacto-N-neotetraose LOS (F62 Delta lgtD), adhered to, and invaded, to the same extent the human cervical epidermoid carcinoma cell line, ME180 [15].

Biological context of YY1

• Inactivation of endogenous YY1 enhances the accumulation of p53 as well as the expression of p53 target genes in response to DNA damage, and it sensitizes cells to DNA damage-induced apoptosis [16].
• Hence, our results demonstrate that YY1 regulates the transcriptional activity, acetylation, ubiquitination, and stability of p53 by inhibiting its interaction with the coactivator p300 and by enhancing its interaction with the negative regulator Mdm2 [16].
• YY1 inhibits the activation of the p53 tumor suppressor in response to genotoxic stress [16].
• Additionally, mutation of the YY1 binding site prevented repression of the promoter by HDAC1 and partially prevented activation of the promoter by trichostatin A [17].
• Our findings suggest that in the natural context, YY1 activity is regulated through intricate mechanisms involving negative feedback loops, histone deacetylation, and recognition of the cognate DNA sequence affected by acetylation and deacetylation of the YY1 protein [18].

Anatomical context of YY1

• This study shows that overexpression of either YY1 or c-Jun represses transcription of the human involucrin gene in multiplying keratinocytes [19].
• YY1 and EZH2 transcripts were additionally detected in metaphase II oocytes [20].
• ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1 [21].
• Oligonucleotides containing this sequence form a specific complex with a nuclear protein extracted from NTera2D1 and Jurkat cells, and with recombinant YY1 produced in E. coli [22].
• We also demonstrated the association between endogenous N1IC and intrinsic YY1 in human acute T-cell lymphoblastic leukemia cell lines [23].

Associations of YY1 with chemical compounds

• Using sucrose gradient centrifugation analysis and immunoprecipitation assays, HCV core was found in a large complex containing B23 and its interacting partner transcription factor YY1 [4].
• The results with protein pull-down experiments are consistent with the hypothesis that interaction of YY1 with c-Jun is an important mechanism for involucrin repression [19].
• Association between YY1 and mammalian RPD3 requires a glycine-rich region on YY1 [24].
• We found that glucose strongly stimulates O-linked N-acetylglucosaminylation (O-GlcNAcylation) on YY1 [25].
• YAF2 appears to have a promyogenic regulatory role, since overexpression of YAF2 in C2 myoblasts stimulates myogenic promoter activity normally restricted by YY1 [26].
• These data indicate that PGF2alpha enhances a direct YY1/StAR promoter interaction and the recruitment of HDAC1 to the promoter, thereby preventing transcriptional activation of the StAR gene [27].

Physical interactions of YY1

• Furthermore, FKBP25 can alter the DNA-binding activity of YY1 [28].
• Here, we demonstrate that the transcription factor Yin Yang 1 (YY1) interacts with p53 and inhibits its transcriptional activity [16].
• The finding that the YY1-binding allele causes a significant increase in CFTR expression in vitro may allow a better understanding of the milder phenotype observed in patients who carry a severe CF mutation within the same gene [29].
• By using yeast three-hybrid assay, we demonstrated that hGABP beta and YY1 formed a complex only in the presence of YEAF1, indicating that YEAF1 is a bridging factor of these two transcription factors [30].
• Individuals bearing haplotypic variants of the MCP-4 core promoter that avidly bind the transcription factor YY-1 had higher plasma levels of MCP-4 than did individuals with variants with lower binding avidity (490, 360, and 360 pg/ml; P < 0.01) [31].

Enzymatic interactions of YY1

• Nuclear cathepsin B-like protease cleaves transcription factor YY1 in differentiated cells [32].
• The best substrates for CPB2.8 Delta CTE were also well hydrolysed by cathepsin L, however, the best inhibitors of the parasite enzyme have low affinity to cathepsin L. These promising data provide leads for the design of anti-parasitic drugs directed against the leishmanial enzyme [33].

Co-localisations of YY1

• Co-immunoprecipitation and immunostaining of cells further indicated that YY1AP co-localizes with YY1 in the nucleus [34].
• PIASy colocalizes with YY1 in the nucleus, stabilizes YY1 in vivo, and differentially regulates YY1 transcriptional activity on different target promoters [35].

Regulatory relationships of YY1

• Consequently, YY1 enhances Mdm2-mediated ubiquitination of p53 [16].
• Here, we present evidence that the activity of YY1 is regulated through acetylation by p300 and PCAF and through deacetylation by HDACs [18].
• YY1 transcription factor down-regulates expression of CCR5, a major coreceptor for HIV-1 [1].
• Increasing doses of a YY-1 expression vector induced significantly greater reporter activity from MCP-4 core promoter expression constructs of the wild-type compared with the variant sequence in transient transfection experiments [31].
• Further, depletion of E2F1 prevented prohibitin from repressing the YY1 promoter [36].

Other interactions of YY1

• Yin Yang 1 is a negative regulator of p53 [7].
• Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function [37].
• We find that expression of YY1 increases occupancy by HDAC1, decreases acetylation at nuc 1, and downregulates LTR expression [38].
• Chromatin immunoprecipitation experiments localized YY1 to the HLA-DRA gene in Rb-defective tumor cells [17].
• A naturally occurring sequence variation that creates a YY1 element is associated with increased cystic fibrosis transmembrane conductance regulator gene expression [29].

Analytical, diagnostic and therapeutic context of YY1

• Electrophoretic mobility shift assays indicate that the -102 site is located in a region of multiple DNA-protein interactions and that the -102A allele recruits specifically an additional nuclear protein related to YY1 [29].
• Fluorescence in situ hybridization with the YY1 clone has localized the YY1 gene to chromosome 14 band q32 [3].
• By competition analysis and use of anti-YY1 antibody in both gel shift and Western blot experiments, we identified the 3beta1-A protein as the ubiquitous transcription factor YY1 [39].
• Transient overexpression and site-directed mutagenesis experiments of the involucrin 5'-non-coding region (5'-NCR) confirmed that YY1 and c-Jun repress involucrin transcription [19].
• Sequence analysis of the HLJ1 gene promoter region showed absence of a TATA box, but identified an inverted CCAAT box and four YY1 transcriptional factor-binding sites, which may be important in the regulation of HLJ1 expression [40].

References