659 Functional Synergy Between Histone Demethylation and Acetylation Defines an Epigenetic Signature for NeuroD Regulated Gene Transcription in Enteroendocrine Cells

Abstract Insulin represses gluconeogenesis, in part, by inhibiting the transcription of genes that encode rate-determining enzymes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). Glucocorticoids stimulate expression of the PEPCK gene but the repressive action of insulin is dominant. Here, we show that treatment of H4IIE hepatoma cells with the synthetic glucocorticoid, dexamethasone (dex), induces the accumulation of glucocorticoid receptor, as well as many transcription factors, coregulators, and RNA polymerase II, on the PEPCK gene promoter. The addition of insulin to dex-treated cells causes the rapid dissociation of glucocorticoid receptor, polymerase II, and several key transcriptional regulators from the PEPCK gene promoter. These changes are temporally related to the reduced rate of PEPCK gene transcription. A similar disruption of the G-6-Pase gene transcription complex was observed. Additionally, insulin causes the rapid demethylation of arginine-17 on histone H3 of both genes. This rapid, insulin-induced, histone demethylation is temporally related to the disruption of the PEPCK and G-6-Pase gene transcription complex, and may be causally related to the mechanism by which insulin represses transcription of these genes.

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Pdx-1 Is Not Sufficient for Repression of Proglucagon Gene Transcription in Islet or Enteroendocrine Cells

Endocrinology ◽

10.1210/en.2004-0495 ◽

2005 ◽

Vol 146 (1) ◽

pp. 441-449 ◽

Cited By ~ 11

Author(s):

Grace Flock ◽

Xiemin Cao ◽

Daniel J. Drucker

Keyword(s):

Gene Expression ◽

Gene Transcription ◽

Nuclear Translocation ◽

Immunohistochemical Analysis ◽

Enteroendocrine Cells ◽

Cell Phenotype ◽

Protein Overexpression ◽

Adenoviral Transduction ◽

Glucagon Like Peptide 1 ◽

The Relationship

Pdx-1 plays a key role in the development of the pancreas and the control of islet gene transcription and has also been proposed as a dominant regulator of the α- vs. β-cell phenotype via extinction of proglucagon expression. To ascertain the relationship between Pdx-1 and proglucagon gene expression, we examined the effect of enhanced pdx-1 expression on proglucagon gene expression in murine islet αTC-1 and GLUTag enteroendocrine cells. Although adenoviral transduction increased the levels of pdx-1 mRNA transcripts and nuclear Pdx-1 protein, overexpression of pdx-1 did not repress endogenous proglucagon gene expression in αTC-1 or GLUTag cells or murine islets. Immunohistochemical analysis of cells transduced with Ad-pdx-1 demonstrated multiple individual islet or enteroendocrine cells exhibiting both nuclear Pdx-1 and cytoplasmic glucagon-like peptide-1 immunopositivity. The failure of pdx-1 to inhibit endogenous proglucagon gene expression was not attributable to defects in Pdx-1 nuclear translocation or DNA binding as demonstrated using Western blotting and EMSA analyses. Furthermore, Ad-pdx-1 transduction did not repress proglucagon promoter activity in αTC-1 or GLUTag cells. Taken together, these findings demonstrate that pdx-1 alone is not sufficient for specification of the hormonal phenotype or extinction of proglucagon gene expression in islet or enteroendocrine cells.

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Activator protein-1 is necessary for angiotensin-II stimulation of human adrenocorticotropin receptor gene transcription

European Journal of Biochemistry ◽

10.1046/j.1432-1033.2001.02055.x ◽

2001 ◽

Vol 268 (6) ◽

pp. 1802-1810

Author(s):

Danielle Naville ◽

Estelle Bordet ◽

Marie-Claude Berthelon ◽

Philippe Durand ◽

Martine Begeot

Keyword(s):

Angiotensin Ii ◽

Gene Transcription ◽

Receptor Gene ◽

Activator Protein 1 ◽

Activator Protein ◽

Stimulation Of

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Regulation of neuronal cholecystokinin gene transcription

CrossRef Listing of Deleted DOIs ◽

10.1080/003655101317095437 ◽

2001 ◽

Vol 61 (7) ◽

pp. 61-67 ◽

Cited By ~ 9

Author(s):

Thomas V. O. Hansen ◽

Finn C. Nielsen

Keyword(s):

Gene Transcription

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Q-mediated late gene transcription of bacteriophage λ: RNA start point and RNase III processing sites in vivo

Virology ◽

10.1016/s0042-6822(88)90119-5 ◽

1988 ◽

Vol 167 (2) ◽

pp. 568-577 ◽

Cited By ~ 1

Author(s):

D DANIELS ◽

M SUBBARAO ◽

F BLATTNER ◽

H LOZERON

Keyword(s):

Gene Transcription ◽

Late Gene ◽

Bacteriophage Λ ◽

Rnase Iii

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Lithium increases cAMP responsive element (CRE)/CRE binding protein directed gene transcription in vitro by enhancing transactivation of transcription

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-2004-819108 ◽

2004 ◽

Vol 112 (S 1) ◽

Author(s):

U Böer ◽

J Eglins ◽

W Knepel

Keyword(s):

Gene Transcription ◽

Binding Protein ◽

Transcription In Vitro ◽

Responsive Element

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GENE ACTIVATION IN MAMMARY CELLS

Acta Endocrinologica ◽

10.1530/acta.0.071s346 ◽

1972 ◽

Vol 71 (2_Suppla) ◽

pp. S346-S368 ◽

Cited By ~ 4

Author(s):

Roger W. Turkington ◽

Nobuyuki Kadohama

Keyword(s):

Cell Differentiation ◽

Gene Transcription ◽

Hormonal Regulation ◽

Gene Activation ◽

Milk Proteins ◽

Mouse Mammary Gland ◽

Nuclear Proteins ◽

Mammary Cells ◽

Alveolar Cells ◽

Mammary Cell

ABSTRACT Hormonal activation of gene transcription has been studied in a model system, the mouse mammary gland in organ culture. Transcriptive activity is stimulated in mammary stem cells by insulin, and in mammary alveolar cells by prolactin and insulin. Studies on the template requirement for expression of the genes for milk proteins demonstrate that DNA methylation has an obligatory dependence upon DNA synthesis, but is otherwise independent from hormonal regulation of mammary cell differentiation. Incorporation of 5-bromo-2′deoxyuridine into DNA selectively inhibits expression of the genes for specific milk proteins. Undifferentiated mammary cells activate the synthesis of specific acidic nuclear proteins when stimulated by insulin. Several of these induced acidic nuclear proteins are undetectable in unstimulated undifferentiated cells, but appear to be characteristic components of the nuclei of differentiated cells. These results indicate that mammary cell differentiation is associated with a change in acidic nuclear proteins, and they provide evidence to support the concept that acidic nuclear proteins may be involved in the regulation of gene transcription and of mammary cell differentiation.

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