Photo-caged agonists of the nuclear receptors RARgamma and TRbeta provide unique time-dependent gene expression profiles for light-activated gene patterning.
Light-activated gene expression systems hold promise as new tools for studying spatial and temporal gene patterning in multicellular systems. Photo-caged forms of nuclear receptor agonists have recently been shown to mediate photo-dependent transcription in mammalian cells, however, because intracellularly released agonists can rapidly diffuse out of cells, the photo-initiated transcription response is only transient and limited to only a few hours in reported examples. Herein we describe a photo-caged thyroid hormone receptor agonist that provides a robust 36 h transcription response to a single irradiation event. These findings are in contrast to a closely related system, which uses a caged retinoic acid receptor agonist, which provides only a short transcription response. Comparison of the two systems, show that the duration of transcription response is not controlled by the rate of diffusion of free ligand out of the cell, but perhaps by the duration of ligand-induced transcription/stability of the active transcription complex.
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Kristian H
KH
Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19176, USA.
Cruz
Federico G
FG
Ye
Hai-Fen
HF
O'reilly
Kathryn E
KE
Dowdell
Sarah
S
Koh
John T
JT
D020869:Gene Expression Profiling / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D010775:Photic Stimulation / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D037042:Thyroid Hormone Receptors beta / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D000097768:Retinoic Acid Receptor gamma
D018168:Receptors, Retinoic Acid; D037042:Thyroid Hormone Receptors beta; D000097768:Retinoic Acid Receptor gamma