Publications by authors named "Yimei Gong"

6 Publications

  • Page 1 of 1

Aiolos promotes anchorage independence by silencing p66Shc transcription in cancer cells.

Cancer Cell 2014 May;25(5):575-89

Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin 300070, China; Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin 300070, China; Laboratory of Epigenetics and Tumorigenesis, Tianjin Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China. Electronic address:

Anchorage of tissue cells to their physical environment is an obligate requirement for survival that is lost in mature hematopoietic and in transformed epithelial cells. Here we find that a lymphocyte lineage-restricted transcription factor, Aiolos, is frequently expressed in lung cancers and predicts markedly reduced patient survival. Aiolos decreases expression of a large set of adhesion-related genes, disrupting cell-cell and cell-matrix interactions. Aiolos also reconfigures chromatin structure within the SHC1 gene, causing isoform-specific silencing of the anchorage reporter p66(Shc) and blocking anoikis in vitro and in vivo. In lung cancer tissues and single cells, p66(Shc) expression inversely correlates with that of Aiolos. Together, these findings suggest that Aiolos functions as an epigenetic driver of lymphocyte mimicry in metastatic epithelial cancers.
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http://dx.doi.org/10.1016/j.ccr.2014.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070880PMC
May 2014

GATA transcription factors regulate LHβ gene expression.

J Mol Endocrinol 2011 Aug 18;47(1):45-58. Epub 2011 Jul 18.

Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.

The GATA family of transcription factors are critical determinants of cell differentiation as well as regulation of adult gene expression throughout the reproductive axis. Within the anterior pituitary gland, GATA factors have been shown to increase glycoprotein α-subunit gene promoter activity; however, nothing has been known about the impact of these factors on expression of the gonadotropin β-subunits. In this study, we demonstrate expression of both GATA2 and GATA4 in primary mouse gonadotropes and the gonadotrope cell line, LβT2. Based on the transient transfection in fibroblast cells, GATA factors increase LH β-subunit gene (LHβ) promoter activity alone and in synergy with the orphan nuclear receptors steroidogenic factor-1 (SF-1) and liver receptor homologue-1 (LRH-1). The GATA response was localized to a DNA regulatory region at position -101 in the rat LHβ gene promoter which overlaps with a previously described cis-element for pituitary homeobox-1 (Pitx1) and is flanked by two SF-1/LRH-1 regulatory sites. As determined by gel shift, GATA and Pitx1 can compete for binding to this element. Furthermore, mutation analysis revealed a requirement for both the GATA/Pitx1 and the SF-1/LRH-1 cis-elements in order to achieve synergy. These studies identify a novel role for GATA transcription factors in the pituitary and reveal additional molecular mechanisms by which precise modulation of LHβ gene expression can be achieved.
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http://dx.doi.org/10.1530/JME-10-0137DOI Listing
August 2011

HNF-1beta regulates transcription of the PKD modifier gene Kif12.

J Am Soc Nephrol 2009 Jan 12;20(1):41-7. Epub 2008 Nov 12.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Hepatocyte nuclear factor-1beta (HNF-1beta) is a transcription factor that regulates gene expression in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1beta lead to a syndrome of inherited renal cysts and diabetes and are also a common cause of sporadic renal dysplasia. The full complement of target genes responsible for the functions of HNF-1beta, however, is incompletely defined. Using a functional genomics approach involving chromatin immunoprecipitation and promoter arrays, combined with gene expression profiling, we found that an HNF-1beta target gene in the kidney is kinesin family member 12 (Kif12), a gene previously identified as a candidate modifier gene in the cpk mouse model of polycystic kidney disease. Mutations of HNF-1beta inhibited Kif12 transcription in both cultured cells and knockout mice by altering co-factor recruitment and histone modification. Because kinesin-12 family members participate in orienting cell division, downregulation of Kif12 may underlie the abnormal planar cell polarity observed in cystic kidney diseases.
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http://dx.doi.org/10.1681/ASN.2008020238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615735PMC
January 2009

Mutations of HNF-1beta inhibit epithelial morphogenesis through dysregulation of SOCS-3.

Proc Natl Acad Sci U S A 2007 Dec 12;104(51):20386-91. Epub 2007 Dec 12.

Departments of Internal Medicine, Molecular Biology, and Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Hepatocyte nuclear factor-1beta (HNF-1beta) is a Pit-1, Oct-1/2, Unc-86 (POU) homeodomain-containing transcription factor expressed in the kidney, liver, pancreas, and other epithelial organs. Mutations of HNF-1beta cause maturity-onset diabetes of the young, type 5 (MODY5), which is characterized by early-onset diabetes mellitus and congenital malformations of the kidney, pancreas, and genital tract. Knockout of HNF-1beta in the mouse kidney results in cyst formation. However, the signaling pathways and transcriptional programs controlled by HNF-1beta are poorly understood. Using genome-wide chromatin immunoprecipitation and DNA microarray (ChIP-chip) and microarray analysis of mRNA expression, we identified SOCS3 (suppressor of cytokine signaling-3) as a previously unrecognized target gene of HNF-1beta in the kidney. HNF-1beta binds to the SOCS3 promoter and represses SOCS3 transcription. The expression of SOCS3 is increased in HNF-1beta knockout mice and in renal epithelial cells expressing dominant-negative mutant HNF-1beta. Increased levels of SOCS-3 inhibit HGF-induced tubulogenesis by decreasing phosphorylation of Erk and STAT-3. Conversely, knockdown of SOCS-3 in renal epithelial cells expressing dominant-negative mutant HNF-1beta rescues the defect in HGF-induced tubulogenesis by restoring phosphorylation of Erk and STAT-3. Thus, HNF-1beta regulates tubulogenesis by controlling the levels of SOCS-3 expression. Manipulating the levels of SOCS-3 may be a useful therapeutic approach for human diseases induced by HNF-1beta mutations.
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http://dx.doi.org/10.1073/pnas.0705957104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2154440PMC
December 2007

Enhanced susceptibility to immune nephritis in DBA/1 mice is contingent upon IL-1 expression.

Clin Immunol 2007 Jul 17;124(1):49-56. Epub 2007 May 17.

Division of Rheumatology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX 75390-8884, USA.

The DBA/1 mouse strain is particularly sensitive to experimental immune-mediated nephritis. Previous studies have indicated that various chemokines/cytokines are elevated in strains of mice susceptible to immune-mediated glomerulonephritis. One of the many elevated cytokines is IL-1. This study was designed to determine if IL-1 is essential for the development of immune-mediated nephritis in the DBA/1 mouse strain that is particularly sensitive to this disease. Both male and female DBA/1 mice and DBA/1.IL-1R1(-/-) mice were challenged with anti-GBM sera. We then compared DBA/1 mice to DBA/1.IL-1R1(-/-) mice to determine the influence of IL-1 on immune-mediated nephritis. Compared to DBA/1 mice, DBA/1.IL-1R1(-/-) mice excreted significantly less protein post anti-GBM serum challenge. None of the DBA/1.IL-1R1(-/-) mice, male or female, had a BUN higher than 22 mg/dl post-challenge whereas wild-type DBA/1 mice had significantly elevated BUN. Wild-type DBA/1 mice exhibited pronounced glomerulonephritis, with crescent formation, as well as tubulo-interstitial disease compared to DBA/1.IL1R1(-/-) mice. These findings indicate that IL-1 is necessary for the development of nephritis in DBA/1 mice and suggest that the elevated IL-1 levels in these mice may be one reason why the DBA/1 strain is particularly sensitive to multiple end organ diseases.
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http://dx.doi.org/10.1016/j.clim.2007.04.002DOI Listing
July 2007

PI3K/AKT/mTOR hypersignaling in autoimmune lymphoproliferative disease engendered by the epistatic interplay of Sle1b and FASlpr.

Int Immunol 2007 Apr 15;19(4):509-22. Epub 2007 Mar 15.

Division of Rheumatology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Previous studies have demonstrated that the NZM2410/NZW 'z' allele of Sle1 on telomeric murine chromosome 1 led to lymphoproliferative autoimmunity, when acting in concert with the FAS(lpr) defect on the C57BL/6 background. The present report shows that the Sle1b sub-locus, harboring the NZM2410/NZW 'z' allele of SLAM, in epistasis with FAS(lpr), may be sufficient to induce lymphoproliferative autoimmunity. Disease in this simplified genetic model is accompanied by significant activation of the AKT signaling axis in both B- and T cells, as evidenced by increased phosphorylation of AKT, mTOR, 4EBP-1 and p70S6K, resulting from increased PI3K and reduced PTEN activity. In addition, blocking this axis using RAD001, an mTOR inhibitor, ameliorated lymphoproliferation and modulated serum IgG anti-nuclear auto-antibodies. Finally, mTOR inhibition also dampened signaling via parallel axes, including the MAPK and NFkB pathways. Hence, hypersignaling via the PI3K/AKT/mTOR axis appears to be an important mechanism underlying autoimmune lymphoproliferative disease, presenting itself as a potential target for therapeutic intervention.
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http://dx.doi.org/10.1093/intimm/dxm017DOI Listing
April 2007