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Your search keyword '"LISA D. NORQUAY"' showing total 2 results
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1. Novel pancreatic endocrine maturation pathways identified by genomic profiling and causal reasoning.

Author

Alex Gutteridge, J Michael Rukstalis, Daniel Ziemek, Mark Tié, Lin Ji, Rebeca Ramos-Zayas, Nancy A Nardone, Lisa D Norquay, Martin B Brenner, Kim Tang, John D McNeish, and Rebecca K Rowntree

Subjects
Medicine, Science
Abstract

We have used a previously unavailable model of pancreatic development, derived in vitro from human embryonic stem cells, to capture a time-course of gene, miRNA and histone modification levels in pancreatic endocrine cells. We investigated whether it is possible to better understand, and hence control, the biological pathways leading to pancreatic endocrine formation by analysing this information and combining it with the available scientific literature to generate models using a casual reasoning approach. We show that the embryonic stem cell differentiation protocol is highly reproducible in producing endocrine precursor cells and generates cells that recapitulate many aspects of human embryonic pancreas development, including maturation into functional endocrine cells when transplanted into recipient animals. The availability of whole genome gene and miRNA expression data from the early stages of human pancreatic development will be of great benefit to those in the fields of developmental biology and diabetes research. Our causal reasoning algorithm suggested the involvement of novel gene networks, such as NEUROG3/E2F1/KDM5B and SOCS3/STAT3/IL-6, in endocrine cell development We experimentally investigated the role of the top-ranked prediction by showing that addition of exogenous IL-6 could affect the expression of the endocrine progenitor genes NEUROG3 and NKX2.2.

Published
2013
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2. RFX1 and NF-1 associate with P sequences of the human growth hormone locus in pituitary chromatin

Author

Lisa D. Norquay, Xiaoyang Yang, Walter Reith, Scott Gregoire, Patricia C. Sheppard, Janice G. Dodd, and Peter A. Cattini

Subjects
CCAAT-Enhancer-Binding Proteins/ metabolism, Molecular Sequence Data, Repressor, Regulatory Factor X Transcription Factors, Chromatin/ metabolism, In Vitro Techniques, ddc:616.07, Placental Hormones/genetics/metabolism, Endocrinology, Binding Sites/physiology, Regulatory Factor X1, Animals, Humans, Transcription Factors/ metabolism, Promoter Regions, Genetic, Molecular Biology, Gene, ChIA-PET, Pituitary Gland/ metabolism, Binding Sites, DNA-Binding Proteins/ metabolism, biology, Base Sequence, Human Growth Hormone, Gene Expression Regulation/physiology, Nuclear Proteins, General Medicine, Human Growth Hormone/ genetics, Molecular biology, Chromatin, Rats, DNA-Binding Proteins, NFI Transcription Factors, Histone, Gene Expression Regulation, Pituitary Gland, CCAAT-Enhancer-Binding Proteins, biology.protein, RFX1, Y-Box-Binding Protein 1, Promoter Regions, Genetic/physiology, Placental Hormones, Oligonucleotide Probes, Chromatin immunoprecipitation, Transcription Factors
Abstract

The human GH family consists of five genes, including the placental chorionic somatomammotropins (CS), within a single locus on chromosome 17. Based on nuclease sensitivity, the entire GH/CS locus is accessible in pituitary chromatin, yet only GH-N is expressed. Previously, we reported a P sequence element (263P) capable of repressing placental CS promoter activity in transfected pituitary (GC) cells. Regions of protein binding within 263P include P sequence elements A and B (PSE-A and PSE-B), and we reported nuclear factor-1 (NF-1) recognition of PSE-B. We now provide evidence for multiple interactions on PSE-A, including binding of the regulatory factor X (RFX) family. Disruption of the RFX site within 263P blunts repressor activity in transfected GC cells; however, repression is only abolished when both PSE-A/RFX and PSE-B/NF-1 sites are mutated. The capacity of RFX and NF-1 to participate in a novel common complex is further suggested by coimmunoprecipitation of RFX1 and epitope-tagged NF-1 family members. Finally, we confirm the association of NF-1 and RFX1 with P sequences in human pituitary tissue by chromatin immunoprecipitation. Taken together, our data suggest that an inverse relationship exists between 263P and CS promoter histone hyperacetylation and the association of these factors in vivo.

Published
2003

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