Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.

Anders Stegmann; Morten Hansen; Yulan Wang; Janus B Larsen; Leif R. Lund; Léa Ritié; Jeremy K Nicholson; Bjørn Quistorff; Patricia Simon-Assmann; Jesper T Troelsen; Jørgen Olsen

doi:10.1152/physiolgenomics.00314.2005

Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.

Anders Stegmann, Morten Hansen, Yulan Wang, Janus B Larsen, Leif R. Lund, Léa Ritié, Jeremy K Nicholson, Bjørn Quistorff, Patricia Simon-Assmann, Jesper T Troelsen, Jørgen Olsen

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Abstract

DNA-binding transcription factors bind to promoters that carry their binding sites. Transcription factors therefore function as nodes in gene regulatory networks. In the present work we used a bioinformatic approach to search for transcription factors that might function as nodes in gene regulatory networks during the differentiation of the small intestinal epithelial cell. In addition we have searched for connections between transcription factors and the villus metabolome. Transcriptome data were generated from mouse small intestinal villus, crypt, and fetal intestinal epithelial cells. Metabolome data were generated from crypt and villus cells. Our results show that genes that are upregulated during fetal to adult and crypt to villus differentiation have an overrepresentation of potential hepatocyte nuclear factor (HNF)-4 binding sites in their promoters. Moreover, metabolome analyses by magic angle spinning (1)H nuclear magnetic resonance spectroscopy showed that the villus epithelial cells contain higher concentrations of lipid carbon chains than the crypt cells. These findings suggest a model where the HNF-4 transcription factor influences the villus metabolome by regulating genes that are involved in lipid metabolism. Our approach also identifies transcription factors of importance for crypt functions such as DNA replication (E2F) and stem cell maintenance (c-Myc).

Original language	English
Journal	Physiological Genomics
Volume	27
Issue number	2
Pages (from-to)	141-55
Number of pages	14
ISSN	1094-8341
DOIs	https://doi.org/10.1152/physiolgenomics.00314.2005
Publication status	Published - 2006

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Stegmann, A., Hansen, M., Wang, Y., Larsen, J. B., Lund, L. R., Ritié, L., Nicholson, J. K., Quistorff, B., Simon-Assmann, P., Troelsen, J. T., & Olsen, J. (2006). Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation. Physiological Genomics, 27(2), 141-55. https://doi.org/10.1152/physiolgenomics.00314.2005

Stegmann, A, Hansen, M, Wang, Y, Larsen, JB, Lund, LR, Ritié, L, Nicholson, JK, Quistorff, B, Simon-Assmann, P, Troelsen, JT & Olsen, J 2006, 'Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.', Physiological Genomics, vol. 27, no. 2, pp. 141-55. https://doi.org/10.1152/physiolgenomics.00314.2005

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title = "Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.",

abstract = "DNA-binding transcription factors bind to promoters that carry their binding sites. Transcription factors therefore function as nodes in gene regulatory networks. In the present work we used a bioinformatic approach to search for transcription factors that might function as nodes in gene regulatory networks during the differentiation of the small intestinal epithelial cell. In addition we have searched for connections between transcription factors and the villus metabolome. Transcriptome data were generated from mouse small intestinal villus, crypt, and fetal intestinal epithelial cells. Metabolome data were generated from crypt and villus cells. Our results show that genes that are upregulated during fetal to adult and crypt to villus differentiation have an overrepresentation of potential hepatocyte nuclear factor (HNF)-4 binding sites in their promoters. Moreover, metabolome analyses by magic angle spinning (1)H nuclear magnetic resonance spectroscopy showed that the villus epithelial cells contain higher concentrations of lipid carbon chains than the crypt cells. These findings suggest a model where the HNF-4 transcription factor influences the villus metabolome by regulating genes that are involved in lipid metabolism. Our approach also identifies transcription factors of importance for crypt functions such as DNA replication (E2F) and stem cell maintenance (c-Myc).",

author = "Anders Stegmann and Morten Hansen and Yulan Wang and Larsen, {Janus B} and Lund, {Leif R.} and L{\'e}a Riti{\'e} and Nicholson, {Jeremy K} and Bj{\o}rn Quistorff and Patricia Simon-Assmann and Troelsen, {Jesper T} and J{\o}rgen Olsen",

note = "Keywords: Algorithms; Animals; Binding Sites; Cell Differentiation; Cloning, Molecular; DNA Replication; DNA, Recombinant; E2F Transcription Factors; Endoderm; Enterocytes; Gene Expression Regulation; Genes, myc; Genomics; Hepatocyte Nuclear Factor 4; Ileum; Intestinal Mucosa; Lipid Metabolism; Magnetic Resonance Spectroscopy; Metalloendopeptidases; Mice; Mice, Inbred C57BL; Microvilli; Models, Genetic; Promoter Regions (Genetics); Proto-Oncogene Proteins c-myc; Stem Cells; Systems Biology; Transcription, Genetic",

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doi = "10.1152/physiolgenomics.00314.2005",

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T1 - Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.

AU - Stegmann, Anders

AU - Hansen, Morten

AU - Wang, Yulan

AU - Larsen, Janus B

AU - Lund, Leif R.

AU - Ritié, Léa

AU - Nicholson, Jeremy K

AU - Quistorff, Bjørn

AU - Simon-Assmann, Patricia

AU - Troelsen, Jesper T

AU - Olsen, Jørgen

N1 - Keywords: Algorithms; Animals; Binding Sites; Cell Differentiation; Cloning, Molecular; DNA Replication; DNA, Recombinant; E2F Transcription Factors; Endoderm; Enterocytes; Gene Expression Regulation; Genes, myc; Genomics; Hepatocyte Nuclear Factor 4; Ileum; Intestinal Mucosa; Lipid Metabolism; Magnetic Resonance Spectroscopy; Metalloendopeptidases; Mice; Mice, Inbred C57BL; Microvilli; Models, Genetic; Promoter Regions (Genetics); Proto-Oncogene Proteins c-myc; Stem Cells; Systems Biology; Transcription, Genetic

PY - 2006

Y1 - 2006

N2 - DNA-binding transcription factors bind to promoters that carry their binding sites. Transcription factors therefore function as nodes in gene regulatory networks. In the present work we used a bioinformatic approach to search for transcription factors that might function as nodes in gene regulatory networks during the differentiation of the small intestinal epithelial cell. In addition we have searched for connections between transcription factors and the villus metabolome. Transcriptome data were generated from mouse small intestinal villus, crypt, and fetal intestinal epithelial cells. Metabolome data were generated from crypt and villus cells. Our results show that genes that are upregulated during fetal to adult and crypt to villus differentiation have an overrepresentation of potential hepatocyte nuclear factor (HNF)-4 binding sites in their promoters. Moreover, metabolome analyses by magic angle spinning (1)H nuclear magnetic resonance spectroscopy showed that the villus epithelial cells contain higher concentrations of lipid carbon chains than the crypt cells. These findings suggest a model where the HNF-4 transcription factor influences the villus metabolome by regulating genes that are involved in lipid metabolism. Our approach also identifies transcription factors of importance for crypt functions such as DNA replication (E2F) and stem cell maintenance (c-Myc).

AB - DNA-binding transcription factors bind to promoters that carry their binding sites. Transcription factors therefore function as nodes in gene regulatory networks. In the present work we used a bioinformatic approach to search for transcription factors that might function as nodes in gene regulatory networks during the differentiation of the small intestinal epithelial cell. In addition we have searched for connections between transcription factors and the villus metabolome. Transcriptome data were generated from mouse small intestinal villus, crypt, and fetal intestinal epithelial cells. Metabolome data were generated from crypt and villus cells. Our results show that genes that are upregulated during fetal to adult and crypt to villus differentiation have an overrepresentation of potential hepatocyte nuclear factor (HNF)-4 binding sites in their promoters. Moreover, metabolome analyses by magic angle spinning (1)H nuclear magnetic resonance spectroscopy showed that the villus epithelial cells contain higher concentrations of lipid carbon chains than the crypt cells. These findings suggest a model where the HNF-4 transcription factor influences the villus metabolome by regulating genes that are involved in lipid metabolism. Our approach also identifies transcription factors of importance for crypt functions such as DNA replication (E2F) and stem cell maintenance (c-Myc).

U2 - 10.1152/physiolgenomics.00314.2005

DO - 10.1152/physiolgenomics.00314.2005

M3 - Journal article

C2 - 16868071

SN - 1094-8341

VL - 27

SP - 141

EP - 155

JO - Physiological Genomics

JF - Physiological Genomics

IS - 2

ER -

Metabolome, transcriptome, and bioinformatic cis-element analyses point to HNF-4 as a central regulator of gene expression during enterocyte differentiation.

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