Publication Date:
2004-02-28
Description:
The transcriptional regulatory networks that specify and maintain human tissue diversity are largely uncharted. To gain insight into this circuitry, we used chromatin immunoprecipitation combined with promoter microarrays to identify systematically the genes occupied by the transcriptional regulators HNF1alpha, HNF4alpha, and HNF6, together with RNA polymerase II, in human liver and pancreatic islets. We identified tissue-specific regulatory circuits formed by HNF1alpha, HNF4alpha, and HNF6 with other transcription factors, revealing how these factors function as master regulators of hepatocyte and islet transcription. Our results suggest how misregulation of HNF4alpha can contribute to type 2 diabetes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012624/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3012624/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Odom, Duncan T -- Zizlsperger, Nora -- Gordon, D Benjamin -- Bell, George W -- Rinaldi, Nicola J -- Murray, Heather L -- Volkert, Tom L -- Schreiber, Jorg -- Rolfe, P Alexander -- Gifford, David K -- Fraenkel, Ernest -- Bell, Graeme I -- Young, Richard A -- N01-DK-9-2310/DK/NIDDK NIH HHS/ -- R01 HG002668/HG/NHGRI NIH HHS/ -- R01 HG002668-01/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 27;303(5662):1378-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14988562" target="_blank"〉PubMed〈/a〉
Keywords:
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
;
Carbohydrate Metabolism
;
*DNA-Binding Proteins
;
Diabetes Mellitus, Type 2/etiology/genetics
;
Gene Expression Profiling
;
*Gene Expression Regulation
;
Genome, Human
;
Gluconeogenesis
;
Hepatocyte Nuclear Factor 1
;
Hepatocyte Nuclear Factor 1-alpha
;
Hepatocyte Nuclear Factor 1-beta
;
Hepatocyte Nuclear Factor 4
;
Hepatocyte Nuclear Factor 6
;
Hepatocytes/*metabolism
;
Homeodomain Proteins/*metabolism
;
Humans
;
Islets of Langerhans/*metabolism
;
Lipid Metabolism
;
*Nuclear Proteins
;
Oligonucleotide Array Sequence Analysis
;
Phosphoproteins/*metabolism
;
Precipitin Tests
;
Promoter Regions, Genetic
;
RNA Polymerase II/metabolism
;
Trans-Activators/*metabolism
;
Transcription Factors/*metabolism
;
Transcription, Genetic
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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