Abstract

The experiments described in this proposal aim to contribute specifically to an understanding of hepatocyte specific gene control. Experiments are described that are aimed both at the signals that trigger and maintain liver-specific expression and the nuclear factors that play a direct role in coordinated hepatocyte expression of a number of genes (al anti- trypsin, transthyretin, albumin and others). In addition to specific expression of some genes in all hepatocytes we will study how certain hepatocytes that are geographically localized for example around the central vein produce particular mRNAs that other hepatocytes do not produce. This kind of information should have wide application in questions related to specific gene expression in other tissues and to specific gene expression during development as well. A fundamental understanding of the mechanisms of normal gene regulation in growing, developing and differentiated cells is widely believed, a belief we share, to be necessary to understand many medical problems including cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA016006-16A1
Application #
3164321
Study Section
Molecular Biology Study Section (MBY)
Project Start
1979-04-01
Project End
1994-03-31
Budget Start
1989-07-01
Budget End
1990-03-31
Support Year
16
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
Graduate Schools
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Song, Jing; Du, Zhanwen; Ravasz, Mate et al. (2015) A Protein Interaction between ?-Catenin and Dnmt1 Regulates Wnt Signaling and DNA Methylation in Colorectal Cancer Cells. Mol Cancer Res 13:969-81
Song, J; Wang, Z; Ewing, R M (2014) Integrated analysis of the Wnt responsive proteome in human cells reveals diverse and cell-type specific networks. Mol Biosyst 10:45-53
Mellacheruvu, Dattatreya; Wright, Zachary; Couzens, Amber L et al. (2013) The CRAPome: a contaminant repository for affinity purification-mass spectrometry data. Nat Methods 10:730-6
Duncan, S A; Zhong, Z; Wen, Z et al. (1997) STAT signaling is active during early mammalian development. Dev Dyn 208:190-8
Zhong, W; Mirkovitch, J; Darnell Jr, J E (1994) Tissue-specific regulation of mouse hepatocyte nuclear factor 4 expression. Mol Cell Biol 14:7276-84
Weinstein, D C; Ruiz i Altaba, A; Chen, W S et al. (1994) The winged-helix transcription factor HNF-3 beta is required for notochord development in the mouse embryo. Cell 78:575-88
Duncan, S A; Manova, K; Chen, W S et al. (1994) Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst. Proc Natl Acad Sci U S A 91:7598-602
Chen, W S; Manova, K; Weinstein, D C et al. (1994) Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos. Genes Dev 8:2466-77
Zhong, W; Sladek, F M; Darnell Jr, J E (1993) The expression pattern of a Drosophila homolog to the mouse transcription factor HNF-4 suggests a determinative role in gut formation. EMBO J 12:537-44
Mirkovitch, J; Darnell Jr, J E (1992) Mapping of RNA polymerase on mammalian genes in cells and nuclei. Mol Biol Cell 3:1085-94

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