Disease relevance of Yy1

• Allele losses at Tcl1, Yy1 genes and D12Mit233 were observed in 94(45%), 143(68%) and 147(70%) of 210 lymphomas, respectively [1].
• We previously reported that YY-1, a versatile transcription factor, regulates expression of glycophorin gene by binding to its locus control region-like region (Gp-LCR) in combination with E-box binding protein during murine erythroleukemia (MEL) cell differentiation [2].
• These studies show that UCRBP binds to various target motifs that are distinct from the UCR motif: the adeno-associated virus P5 promoter and elements in the immunoglobulin light- and heavy-chain genes, as well as elements in ribosomal protein genes [3].
• The 2.4-kb UCRBP message is expressed in all cell lines examined (teratocarcinoma, B- and T-cell, macrophage, fibroblast, and myocyte), consistent with the ubiquitous expression of the UCR-binding factor [3].
• Infection of HC11 cells with a YY1-expressing recombinant retrovirus resulted in overexpression of YY1 but did not suppress hormonal induction [4].

Psychiatry related information on Yy1

• However, all mutants induced disease with slightly shorter latency periods than the wt SL3-3, suggesting that the YY1 motif as well as its immediate context in the UCR have a negative effect on the pathogenicity of the virus [5].

High impact information on Yy1

• The yeast two-hybrid system was used to screen a human complementary DNA (cDNA) library for proteins that associate with YY1, and a c-myc cDNA was isolated [6].
• In undifferentiated myoblasts, endogenous Ezh2 was associated with the transcriptional regulator YY1 [7].
• Upon gene activation, Ezh2, HDAC1, and YY1 dissociated from muscle loci, H3-K27 became hypomethylated and MyoD and SRF were recruited to the chromatin [7].
• The pTalpha enhancer appears to function preferentially in pre-T cell lines and binds multiple nuclear factors, including YY1 [8].
• YY1 binds to both the AN enhancer and promoter region [9].

Biological context of Yy1

• Mutation analysis revealed two YY1 core binding sites at -40/-37 bp (YY1A) and, on the reverse strand, at -32/-29 bp (YY1B) immediately adjacent to the TATA box [10].
• Mutation of the TATA box to TgTA enhanced YY1 complex formation [10].
• The Col1a1 promoter region spanning base pairs (bp) -56 to -9 bound purified recombinant YY1 and the corresponding binding activity in nuclear extracts was supershifted using a YY1-specific antibody [10].
• These findings suggest that YY1 contributes to specific loricrin gene expression in differentiated keratinocytes by suppression of its transcription in undifferentiated keratinocytes [11].
• Negative regulatory factors are also known to play a role in cholesterol homeostasis, and the ubiquitous Yin Yang-1 zinc finger transcription factor (YY1) has been shown to repress several sterol-responsive gene promoters [12].

Anatomical context of Yy1

• Our results indicate that YY1 binds to the Col1a1 proximal promoter and functions as a positive regulator of constitutive activity in fibroblasts [10].
• Furthermore, we demonstrated that forced expression of YY1 in differentiated keratinocytes results in specific downregulation of expression of other early and late differentiation markers [11].
• We find that SNAP(c) purified from cell lines expressing tagged SNAP(c) subunits is associated with Yin Yang-1 (YY1), a factor implicated in both activation and repression of transcription [13].
• In semi-quantitative analysis of Yy1 mRNA levels by RT-PCR, kinetics of the yield of the Yy1-cDNA-specific PCR products showed almost the same profiles among thymic lymphomas with allelic loss at Yy1, lymphomas with both alleles retained and normal thymus [1].
• In similar experiments on primary bone marrow cells, enforced YY1 expression blocked the outgrowth of CFU-GM colonies [14].

Associations of Yy1 with chemical compounds

• Yin yang 1 protein negatively regulates high-density lipoprotein receptor gene transcription by disrupting binding of sterol regulatory element binding protein to the sterol regulatory element [12].
• Involvement of YY1 and its correlation with c-myc in NDEA induced hepatocarcinogenesis, its prevention by d-limonene [15].
• Western blot analysis has shown inhibition of YY1 protein in NDEA induced liver tumor samples in comparison to normal and both NDEA and limonene treated samples [15].
• To work further in this direction, an attempt has been made here to know the role of YY1 (Yin Yang 1) transcription factor in N-nitrodiethylamine (NDEA) induced hepatocarcinogenesis and its chemoprevention by d-limonene [15].
• YY1 is involved in RANKL-induced transcription of the tartrate-resistant acid phosphatase gene in osteoclast differentiation [16].

Physical interactions of Yy1

• As these two factors are able to mediate opposing transcriptional effects by reorganizing the local chromatin environment, the relative levels of NFY and YY1 binding could represent a mechanism for balancing activation and repression of Hoxb4 through the same site [17].
• In addition, YY1 bound specifically to three YY1 binding sites on the proximal promoter of Msx2 that accounted for this transactivation [18].
• We have also investigated the mechanism by which association with c-Myc inhibits YY1's ability to regulate transcription. c-Myc does not block binding of YY1 to DNA [19].
• This finding indicates that MGF regulates the DNA binding activity of YY1 and thereby may cause the relief of transcriptional repression [4].
• DNA-protein binding by gel mobility shift and methylation interference analyses indicated that the pyrimidine-rich sequence immediately flanking the transcription start site consists of an NF-E1 factor binding motif with an overlapping upstream Sp1 binding site [20].

Regulatory relationships of Yy1

• Yin-yang 1 negatively regulates the differentiation-specific transcription of mouse loricrin gene in undifferentiated keratinocytes [11].
• However, along with our earlier information about c-myc with the present study, clearly indicated the involvement of YY1 in NDEA induced hepatocarcinogenesis and d-limonene mediated chemoprevention which might be regulated by c-myc oncoprotein [15].
• To test the hypothesis that YY1 regulates Msx2 gene expression, P19 embryonal cells were used in a number of expression and binding assays [18].
• Overexpression of YY1 strongly repressed the transcriptional capacity of a stably integrated IFN-beta promoter fused to a chloramphenicol acetyltransferase reporter gene as well as the endogenous IFN activity of murine L929 cells via an HDAC activity [21].
• Expression of Pax2 in the intermediate mesoderm is regulated by YY1 [22].

Other interactions of Yy1

• YY1 was able to attenuate the transcriptional synergy caused by the combined actions of SREBP-1a and Sp1 [12].
• However, YY1 was still an efficient transcriptional repressor for SREBP-1a-induced activation [12].
• YY1 is a positive regulator of transcription of the Col1a1 gene [10].
• Using fluorescence in situ hybridization, we have localized Stat5a to rat chromosome band 10q32.1 and Yy1 to rat chromosome band 6q32 [23].
• These results suggest that Tcl1, Yy1 and Tnfalphaip2 genes are not predominantly involved in radiation lymphomagenesis of mice [1].

Analytical, diagnostic and therapeutic context of Yy1

• Western blotting and immunohistochemical analyses indicated that YY1 is more abundant in undifferentiated than in differentiated keratinocytes [11].
• Electrophoretic mobility shift assay results have clearly indicated the binding of YY1 in control liver tissue [15].
• On the otherhand RT-PCR analysis does not indicate any correlation between YY1 mRNA level and inhibition of YY1 protein [15].
• Affinity chromatography confirmed that YY1 associates with c-Myc but not with Max [6].
• To determine the biological role of YY1 in mammalian development, we generated mice deficient for YY1 by gene targeting [24].

References