Assembly of the Yin Yang 1 Transcription Factor into Messenger Ribonucleoprotein Particles Requires Direct RNA Binding Activity

YY1 (Yin Yang 1) is present in the Xenopus oocyte cytoplasm as a constituent of messenger ribonucleoprotein complexes (mRNPs). Association of YY1 with mRNPs requires direct RNA-binding activity. Previously, we have shown YY1 has a high affinity for U-rich RNA; however, potential interactions with plausible in vivo targets have not been investigated. Here we report a biochemical characterization of the YY1–RNA interaction including an investigation of the stability, potential 5′-methylguanosine affinity, and specificity for target RNAs. The formation of YY1–RNA complexes in vitro was highly resistant to thermal, ionic, and detergent disruption. The endogenous oocyte YY1–mRNA interactions were also found to be highly stable. Specific YY1–RNA interactions were observed with selected mRNA and 5S RNA probes. The affinity of YY1 for these substrates was within an order of magnitude of that for its cognate DNA element. Experiments aimed at determining the potential role of the 7-methylguanosine cap on RNA-binding reveal no significant difference in the affinity of YY1 for capped or uncapped mRNA. Taken together, the results show that the YY1–RNA interaction is highly stable, and that YY1 possesses the ability to interact with structurally divergent RNA substrates. These data are the first to specifically document the interaction between YY1 and potential in vivo targets.

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The transcription factor Yin Yang 1 is an activator of BACE1 expression

Journal of Neurochemistry ◽

10.1111/j.1471-4159.2006.03692.x ◽

2006 ◽

Vol 96 (6) ◽

pp. 1696-1707 ◽

Cited By ~ 50

Author(s):

Katrin Nowak ◽

Christine Lange-Dohna ◽

Ulrike Zeitschel ◽

Albrecht Günther ◽

Bernhard Lüscher ◽

...

Keyword(s):

Transcription Factor ◽

Yin Yang 1 ◽

Bace1 Expression ◽

Yin Yang

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Astrocyte-specific deletion of the transcription factor Yin Yang 1 in murine substantia nigra mitigates manganese-induced dopaminergic neurotoxicity

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.015552 ◽

2020 ◽

Vol 295 (46) ◽

pp. 15662-15676 ◽

Cited By ~ 1

Author(s):

Edward Pajarillo ◽

James Johnson ◽

Asha Rizor ◽

Ivan Nyarko-Danquah ◽

Getinet Adinew ◽

...

Keyword(s):

Transcription Factor ◽

Substantia Nigra ◽

Critical Role ◽

Conditional Knockout ◽

Motor Functions ◽

Mn Toxicity ◽

Protein Levels ◽

Yin Yang 1 ◽

Yin Yang

Manganese (Mn)-induced neurotoxicity resembles Parkinson's disease (PD), but the mechanisms underpinning its effects remain unknown. Mn dysregulates astrocytic glutamate transporters, GLT-1 and GLAST, and dopaminergic function, including tyrosine hydroxylase (TH). Our previous in vitro studies have shown that Mn repressed GLAST and GLT-1 via activation of transcription factor Yin Yang 1 (YY1). Here, we investigated if in vivo astrocytic YY1 deletion mitigates Mn-induced dopaminergic neurotoxicity, attenuating Mn-induced reduction in GLAST/GLT-1 expression in murine substantia nigra (SN). AAV5-GFAP-Cre-GFP particles were infused into the SN of 8-week–old YY1flox/flox mice to generate a region-specific astrocytic YY1 conditional knockout (cKO) mouse model. 3 weeks after adeno-associated viral (AAV) infusion, mice were exposed to 330 μg of Mn (MnCl2 30 mg/kg, intranasal instillation, daily) for 3 weeks. After Mn exposure, motor functions were determined in open-field and rotarod tests, followed by Western blotting, quantitative PCR, and immunohistochemistry to assess YY1, TH, GLAST, and GLT-1 levels. Infusion of AAV5-GFAP-Cre-GFP vectors into the SN resulted in region-specific astrocytic YY1 deletion and attenuation of Mn-induced impairment of motor functions, reduction of TH-expressing cells in SN, and TH mRNA/protein levels in midbrain/striatum. Astrocytic YY1 deletion also attenuated the Mn-induced decrease in GLAST/GLT-1 mRNA/protein levels in midbrain. Moreover, YY1 deletion abrogated its interaction with histone deacetylases in astrocytes. These results indicate that astrocytic YY1 plays a critical role in Mn-induced neurotoxicity in vivo, at least in part, by reducing astrocytic GLAST/GLT-1. Thus, YY1 might be a potential target for treatment of Mn toxicity and other neurological disorders associated with dysregulation of GLAST/GLT-1.

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Repression of the Steroidogenic Acute Regulatory Gene by the Multifunctional Transcription Factor Yin Yang 1

Endocrinology ◽

10.1210/endo.143.3.8668 ◽

2002 ◽

Vol 143 (3) ◽

pp. 1085-1096 ◽

Cited By ~ 23

Author(s):

Anna C. Nackley ◽

Wendy Shea-Eaton ◽

Dayami Lopez ◽

Mark P. McLean

Keyword(s):

Transcription Factor ◽

Regulatory Gene ◽

Yin Yang 1 ◽

Yin Yang ◽

Steroidogenic Acute Regulatory ◽

Multifunctional Transcription Factor

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Inhibition of the transcription factor Yin Yang 1 activity by S-nitrosation

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2005.08.150 ◽

2005 ◽

Vol 336 (2) ◽

pp. 692-701 ◽

Cited By ~ 58

Author(s):

Fumiya Hongo ◽

Hermes Garban ◽

Sara Huerta-Yepez ◽

Mario Vega ◽

Ali R. Jazirehi ◽

...

Keyword(s):

Transcription Factor ◽

Yin Yang 1 ◽

Yin Yang

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Regulation of Transcription Factor Yin Yang 1 by SET7/9-mediated Lysine Methylation

Scientific Reports ◽

10.1038/srep21718 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 16

Author(s):

Wen-juan Zhang ◽

Xiao-nan Wu ◽

Tao-tao Shi ◽

Huan-teng Xu ◽

Jia Yi ◽

...

Keyword(s):

Transcription Factor ◽

Regulation Of Transcription ◽

Lysine Methylation ◽

Yin Yang 1 ◽

Yin Yang

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Regulation of the Transcription Factor YY1 in Mitosis through Phosphorylation of Its DNA-binding Domain

Molecular Biology of the Cell ◽

10.1091/mbc.e09-04-0264 ◽

2009 ◽

Vol 20 (22) ◽

pp. 4766-4776 ◽

Cited By ~ 52

Author(s):

Raed Rizkallah ◽

Myra M. Hurt

Keyword(s):

Transcription Factor ◽

Dna Binding ◽

Binding Activity ◽

Binding Domain ◽

Phosphorylation Sites ◽

Dna Binding Domain ◽

Daughter Cells ◽

Dna Binding Activity ◽

Yin Yang 1 ◽

Transcription Factor Yy1

Yin-Yang 1 (YY1) is a ubiquitously expressed zinc finger transcription factor. It regulates a vast array of genes playing critical roles in development, differentiation, and cell cycle. Very little is known about the mechanisms that regulate the functions of YY1. It has long been proposed that YY1 is a phosphoprotein; however, a direct link between phosphorylation and the function of YY1 has never been proven. Investigation of the localization of YY1 during mitosis shows that it is distributed to the cytoplasm during prophase and remains excluded from DNA until early telophase. Immunostaining studies show that YY1 is distributed equally between daughter cells and rapidly associates with decondensing chromosomes in telophase, suggesting a role for YY1 in early marking of active and repressed genes. The exclusion of YY1 from DNA in prometaphase HeLa cells correlated with an increase in the phosphorylation of YY1 and loss of DNA-binding activity that can be reversed by dephosphorylation. We have mapped three phosphorylation sites on YY1 during mitosis and show that phosphorylation of two of these sites can abolish the DNA-binding activity of YY1. These results demonstrate a novel mechanism for the inactivation of YY1 through phosphorylation of its DNA-binding domain.

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Essential Dosage-Dependent Functions of the Transcription Factor Yin Yang 1 in Late Embryonic Development and Cell Cycle Progression

Molecular and Cellular Biology ◽

10.1128/mcb.26.9.3565-3581.2006 ◽

2006 ◽

Vol 26 (9) ◽

pp. 3565-3581 ◽

Cited By ~ 119

Author(s):

El Bachir Affar ◽

Frédérique Gay ◽

Yujiang Shi ◽

Huifei Liu ◽

Maite Huarte ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Transcription Factor ◽

Cell Cycle Progression ◽

Target Genes ◽

Eukaryotic Cell ◽

Dependent Manner ◽

Phenotypic Analysis ◽

Yin Yang 1 ◽

Yin Yang

ABSTRACT Constitutive ablation of the Yin Yang 1 (YY1) transcription factor in mice results in peri-implantation lethality. In this study, we used homologous recombination to generate knockout mice carrying yy1 alleles expressing various amounts of YY1. Phenotypic analysis of yy1 mutant embryos expressing ∼75%, ∼50%, and ∼25% of the normal complement of YY1 identified a dosage-dependent requirement for YY1 during late embryogenesis. Indeed, reduction of YY1 levels impairs embryonic growth and viability in a dose-dependent manner. Analysis of the corresponding mouse embryonic fibroblast cells also revealed a tight correlation between YY1 dosage and cell proliferation, with a complete ablation of YY1 inducing cytokinesis failure and cell cycle arrest. Consistently, RNA interference-mediated inhibition of YY1 in HeLa cells prevents cytokinesis, causes proliferative arrest, and increases cellular sensitivity to various apoptotic agents. Genome-wide expression profiling identified a plethora of YY1 target genes that have been implicated in cell growth, proliferation, cytokinesis, apoptosis, development, and differentiation, suggesting that YY1 coordinates multiple essential biological processes through a complex transcriptional network. These data not only shed new light on the molecular basis for YY1 developmental roles and cellular functions, but also provide insight into the general mechanisms controlling eukaryotic cell proliferation, apoptosis, and differentiation.

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