Yin-Yang 1 Negatively Regulates the Differentiation-Specific Transcription of Mouse Loricrin Gene in Undifferentiated Keratinocytes

Xu, Xuezhu; Kawachi, Yasuhiro; Nakamura, Yasuhiro; Sakurai, Hideko; Hirota, Ayako; Banno, Tomohiro; Takahashi, Takenori; Roop, Dennis R.; Otsuka, Fujio

doi:10.1111/j.0022-202x.2004.23492.x

Cited by 17 publications

(17 citation statements)

References 31 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, an antibody directed against YY1, but not SP1, disrupted the putative YY1-DNA binding complex, suggesting that the complex contained the YY1 transcription factor. Disruption of the binding complex by the YY1 antibody has been reported previously 21–23and similar findings were obtained using 35S labeled recombinant YY1 (Supplemental Fig. S1, please see http://hyper.ahajournals.org.…”

Section: Resultssupporting

confidence: 86%

Endothelin-Stimulated Human B-Type Natriuretic Peptide Gene Expression Is Mediated by Yin Yang 1 in Association With Histone Deacetylase 2

et al. 2009

View full text Add to dashboard Cite

Abstract-Increased B-type natriuretic peptide (BNP) gene expression is regarded as one of the hallmarks of cardiac myocyte hypertrophy. Here we demonstrate that both basal-and endothelin-1-dependent stimulation of human (h) BNP gene transcription requires the presence of an intact Yin Yang 1 (YY1) binding site positioned at Ϫ62 bp relative to the transcription start site. Mutation of this site reduced both basal and stimulated hBNP promoter activity. This site was shown to bind YY1 both in vitro and within the context of the intact cell. The latter interaction increased after endothelin-1 treatment. Exposure to endothelin-1 also resulted in increased nuclear localization of YY1 and a reduction in acetylation of the YY1 protein. Overexpression of wild-type YY1 increased both basal and endothelin-stimulated hBNP promoter activity, whereas a carboxy-terminal deletion mutant of YY1 was devoid of activity. Treatment with the histone deacetylase inhibitor trichostatin A resulted in decreased hBNP reporter activity. YY1 was shown to associate with histone deacetylase 2, and histone deacetylase 2 was shown to associate directly with the hBNP promoter in the intact cell. Collectively these findings demonstrate that YY1 plays an important role in regulating the transcriptional activity of the hBNP gene promoter. These data suggest a model in which YY1 activates hBNP transcription through interaction with histone deacetylase 2. (Hypertension. 2009;53:549-555.)Key Words: B-type natriuretic peptide Ⅲ cardiac hypertrophy Ⅲ endothelin Ⅲ histone deacetylase Ⅲ Ying Yang 1 C ardiac hypertrophy is characterized by both positive and negative changes in the gene expression profile of the heart. 1,2 Increased expression of the cardiac natriuretic peptides, atrial natriuretic peptide and brain or B-type natriuretic peptide (BNP), has been linked to the development of hypertrophy in both animal models and humans. 3,4 Atrial natriuretic peptide and BNP both possess potent activity in the cardiovascular and renal systems. Through association with a shared receptor, they each reduce blood pressure; maintain or improve glomerular filtration rate; promote a natriuretic diuresis; inhibit secretion and/or action of vasopressin, renin, angiotensin, and aldosterone; and suppress hypertrophy, hyperplasia, and/or fibrosis in the heart and vasculature. 5 Thus, they function as endogenous antagonists of many of the factors that have been causally linked to the pathogenesis of human cardiovascular disease.Under normal conditions, BNP is expressed at relatively low levels in the adult heart and without a pronounced chamber-specific pattern. Expression is increased in late fetal and early neonatal life, and it increases dramatically in association with cardiac hypertrophy. Plasma BNP levels are used clinically in the diagnosis and management of heart failure. 6,7 The transcription factor Ying Yang 1 (YY1), also known as NF-F1, UCRBP, and CF1, is a ubiquitously expressed 68-kDa, zinc-finger transcription factor of the GLI-Kruppel family with the relati...

show abstract

Section: Resultssupporting

confidence: 86%

Endothelin-Stimulated Human B-Type Natriuretic Peptide Gene Expression Is Mediated by Yin Yang 1 in Association With Histone Deacetylase 2

et al. 2009

View full text Add to dashboard Cite

show abstract

“…It is also consistent with the downregulation of LOR described by Hohl [26], who also noticed the similarity between FLG and LOR expression changes. This change may be important in light of the well-known strict regulation of the LOR gene at the transcriptional level [15, 27]. In situ hybridization analyses have shown that LOR transcripts are localized only in the upper spinous and granular layers of the normal epidermis [28].…”

Section: Discussionmentioning

confidence: 99%

Locus 1q21 Gene Expression Changes in Atopic Dermatitis Skin Lesions: Deregulation of Small Proline-Rich Region 1A

Jarząb

Filipowska

Zebracka

et al. 2009

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Background: Discovery of the significant impact of filaggrin (FLG) mutations on the genetic predisposition to atopic dermatitis (AD) focused attention on the 1q21 locus, where not only FLG but also other epidermal genes are located. In the present study, we compared 1q21 gene expression in lesional versus nonlesional AD skin. Methods: A real-time quantitative PCR analysis of 10 1q21 genes, selected on the basis of a previous microarray study, was performed in skin biopsies from 33 individuals with AD. Three alternative pathway keratins were also evaluated. Results: In chronic AD skin lesions, we observed an increase in RNA encoding involucrin, S100 calcium-binding proteins A2 and A7–A9 and small proline-rich region (SPRR) proteins 1A and 2C, with fold changes ranging from 2.0 for S100A2 to 15.4 for S100A8 (p < 0.001, Bonferroni corrected), in parallel to the overexpression of the alternative pathway keratins 6A, 6B and 16. The loricrin (LOR) expression level was significantly decreased in lesional AD skin (fold change 0.5; p < 0.01). The expression of the majority of 1q21 genes and alternative keratins was closely correlated; however, for SPRR1A (and SPRR2C) in lesional skin, the correlation with other genes was lost. Conclusions: We hypothesize that the deregulated increase in SPRR1A expression in chronic atopic skin lesions reflects an insufficient rise in SPRR transcripts, unable to compensate for the lack of LOR and thus contributing to the persistence of chronic AD skin lesions. Turning off the stress response in the skin may be regarded as a goal in the treatment of AD skin lesions, and SPRR genes might be targets for such an approach.

show abstract

“…Further, a potential binding site for YY1 was found. YY1 is a prominent repressor of transcription, also in epidermal cells (69,70). Neither repressor has yet been connected to HH/GLI signaling, and additional studies are necessary to address their potential involvement in the repression of FST expression.…”

Section: Discussionmentioning

confidence: 99%

GLI2-specific Transcriptional Activation of the Bone Morphogenetic Protein/Activin Antagonist Follistatin in Human Epidermal Cells

Eichberger

Kaser

Pixner

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hedgehog (HH) signaling in the epidermis is primarily mediated by the zinc finger transcription factors GLI1 and GLI2. Exquisite regulation of HH/GLI signaling is crucial for proper specification of the epidermal lineage and development of its derivatives, whereas dysregulation of HH/GLI signaling disrupts tissue homeostasis and causes basal cell carcinoma (BCC). Similarly, bone morphogenetic proteins (BMPs) and activins have been described as key signaling factors in the complex regulation of epidermal fate decisions, although their precise interplay with HH/GLI is largely elusive. Here we show that, in human epidermal cells, expression of the activin/BMP antagonist follistatin (FST) is predominantly up-regulated by the HH effector GLI2. Consistently, we found strong FST expression in the outer root sheath of human hair follicles and BCC. Detailed promoter analysis showed that two sequences with homology to the GLI consensus binding site are required for GLI2-mediated activation. Interestingly, activation of the FST promoter is highly GLI2-specific, because neither GLI1 nor GLI3 can significantly increase FST transcription. GLI2 specificity requires the presence of a 518-bp fragment in the proximal FST promoter region. On the protein level, sequences C-terminal to the zinc finger are responsible for GLI2-specific activation of FST transcription, pointing to the existence of GLI-interacting cofactors that modulate GLI target specificity. Our results reveal a key role of GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling and provide new evidence for a regulatory interaction between HH and activin/BMP signaling in hair follicle development and BCC.

show abstract

Yin-Yang 1 Negatively Regulates the Differentiation-Specific Transcription of Mouse Loricrin Gene in Undifferentiated Keratinocytes

Cited by 17 publications

References 31 publications

Endothelin-Stimulated Human B-Type Natriuretic Peptide Gene Expression Is Mediated by Yin Yang 1 in Association With Histone Deacetylase 2

Endothelin-Stimulated Human B-Type Natriuretic Peptide Gene Expression Is Mediated by Yin Yang 1 in Association With Histone Deacetylase 2

Locus 1q21 Gene Expression Changes in Atopic Dermatitis Skin Lesions: Deregulation of Small Proline-Rich Region 1A

GLI2-specific Transcriptional Activation of the Bone Morphogenetic Protein/Activin Antagonist Follistatin in Human Epidermal Cells

Contact Info

Product

Resources

About