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

Partial promoter substitutions generating transcriptional sentinels of diverse signaling pathways in embryonic stem cells and mice.
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DOI:
10.1242/dmm.009696
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发表时间:
2012-11
影响因子:
4.3
通讯作者:
Zaret KS
Zaret KS
中科院分区:
医学2区
文献类型:
--
作者:
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 JM;Macdonald RJ;Grapin-Botton A;Magnuson MA;Zaret KS

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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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