Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

Palle Serup; Carsten Gustavsen; Tino Klein; Leah A Potter; Robert Lin; Nandita Mullapudi; Ewa Wandzioch; Angela Hines; Ashley Davis; Christine Bruun; Nina Engberg; Dorthe R Petersen; Janny M L Peterslund; Raymond J Macdonald; Anne Grapin-Botton; Mark A Magnuson; Kenneth S Zaret

doi:10.1242/dmm.009696

Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

Palle Serup, Carsten Gustavsen, Tino Klein, Leah A Potter, Robert Lin, Nandita Mullapudi, Ewa Wandzioch, Angela Hines, Ashley Davis, Christine Bruun, Nina Engberg, Dorthe R Petersen, Janny M L Peterslund, Raymond J Macdonald, Anne Grapin-Botton, Mark A Magnuson, Kenneth S Zaret

10 Citations (Scopus)

Abstract

Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent of different signals in different cellular contexts. We used recombinase-mediated cassette exchange (RMCE) to test the effect of successively deleting conserved genomic regions of the ubiquitously active Rosa26 promoter and substituting the deleted regions for regulatory sequences that respond to diverse extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can be adapted to any pathway that acts via DNA elements.

Original language	English
Journal	Disease Models and Mechanisms
Volume	5
Issue number	6
Pages (from-to)	956-66
Number of pages	11
ISSN	1754-8403
DOIs	https://doi.org/10.1242/dmm.009696
Publication status	Published - 1 Nov 2012

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10.1242/dmm.009696

http://www.ncbi.nlm.nih.gov/pubmed/22888097

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Serup, P., Gustavsen, C., Klein, T., Potter, L. A., Lin, R., Mullapudi, N., Wandzioch, E., Hines, A., Davis, A., Bruun, C., Engberg, N., Petersen, D. R., Peterslund, J. M. L., Macdonald, R. J., Grapin-Botton, A., Magnuson, M. A., & Zaret, K. S. (2012). Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice. Disease Models and Mechanisms, 5(6), 956-66. https://doi.org/10.1242/dmm.009696

Serup, P, Gustavsen, C, Klein, T, Potter, LA, Lin, R, Mullapudi, N, Wandzioch, E, Hines, A, Davis, A, Bruun, C, Engberg, N, Petersen, DR, Peterslund, JML, Macdonald, RJ, Grapin-Botton, A, Magnuson, MA & Zaret, KS 2012, 'Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice', Disease Models and Mechanisms, vol. 5, no. 6, pp. 956-66. https://doi.org/10.1242/dmm.009696

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abstract = "Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent of different signals in different cellular contexts. We used recombinase-mediated cassette exchange (RMCE) to test the effect of successively deleting conserved genomic regions of the ubiquitously active Rosa26 promoter and substituting the deleted regions for regulatory sequences that respond to diverse extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can be adapted to any pathway that acts via DNA elements.",

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AU - Serup, Palle

AU - Gustavsen, Carsten

AU - Klein, Tino

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AU - Lin, Robert

AU - Mullapudi, Nandita

AU - Wandzioch, Ewa

AU - Hines, Angela

AU - Davis, Ashley

AU - Bruun, Christine

AU - Engberg, Nina

AU - Petersen, Dorthe R

AU - Peterslund, Janny M L

AU - Macdonald, Raymond J

AU - Grapin-Botton, Anne

AU - Magnuson, Mark A

AU - Zaret, Kenneth S

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N2 - Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent of different signals in different cellular contexts. We used recombinase-mediated cassette exchange (RMCE) to test the effect of successively deleting conserved genomic regions of the ubiquitously active Rosa26 promoter and substituting the deleted regions for regulatory sequences that respond to diverse extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can be adapted to any pathway that acts via DNA elements.

AB - Extracellular signals in development, physiology, homeostasis and disease often act by regulating transcription. Herein we describe a general method and specific resources for determining where and when such signaling occurs in live animals and for systematically comparing the timing and extent of different signals in different cellular contexts. We used recombinase-mediated cassette exchange (RMCE) to test the effect of successively deleting conserved genomic regions of the ubiquitously active Rosa26 promoter and substituting the deleted regions for regulatory sequences that respond to diverse extracellular signals. We thereby created an allelic series of embryonic stem cells and mice, each containing a signal-responsive sentinel with different fluorescent reporters that respond with sensitivity and specificity to retinoic acids, bone morphogenic proteins, activin A, Wnts or Notch, and that can be adapted to any pathway that acts via DNA elements.

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DO - 10.1242/dmm.009696

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Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice

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