tailieunhanh - Báo cáo khoa học: RE-1 silencing transcription factor (REST) regulates human synaptophysin gene transcription through an intronic sequence-specific DNA-binding site Michael Lietz, Mathias Hohl and Gerald Thiel Department of Medical Biochemistry and Molecular

Synaptophysin, one of the major proteins on synaptic vesi-cles, is ubiquitously expressed throughout the brain. Syn-aptophysin and synapsin I, another synaptic vesicle protein, are also expressed by retinoic acid-induced neuronally dif-ferentiated P19 teratocarcinoma cells. Here, we show that inhibition of histone deacetylase activity in P19 cells is suf-ficient to activate transcription of the synaptophysin and synapsin I genes, indicating that neuronal differentiation and impairment of histone deacetylases results in a similar gene expression pattern | Eur. J. Biochem. 270 2-9 2003 FEBS 2003 doi RE-1 silencing transcription factor REST regulates human synaptophysin gene transcription through an intronic sequence-specific DNA-binding site Michael Lietz Mathias Hohl and Gerald Thiel Department of Medical Biochemistry and Molecular Biology University of Saarland Medical Center Homburg Germany Synaptophysin one of the major proteins on synaptic vesicles is ubiquitously expressed throughout the brain. Syn-aptophysin and synapsin I another synaptic vesicle protein are also expressed by retinoic acid-induced neuronally differentiated P19 teratocarcinoma cells. Here we show that inhibition of histone deacetylase activity in P19 cells is sufficient to activate transcription of the synaptophysin and synapsin I genes indicating that neuronal differentiation and impairment of histone deacetylases results in a similar gene expression pattern. The transcription factor REST a repressor of neuronal genes in non-neuronal tissues has been shown to function via recruitment of histone deacetylases to the transcription unit indicating that modulation of the chromatin structure via histone deacetylation is of major importance for REST function and neuron-specific gene transcription. Furthermore REST has been shown to be the major regulator of neuronal expression of synapsin I. Here we have identified a functional binding site for REST in the first intron of the human synaptophysin gene indicating that REST blocks human synaptophysin gene transcription through an intronic neuron-specific silencer element. The synaptophysin promoter is however devoid of neuronspecific genetic elements and directs transcription in both neuronal and non-neuronal cells. Using a dominant-negative approach we have identified the transcription factor Sp1 as one of the regulators responsible for constitutive transcription of the human synaptophysin gene. Keywords neuronal genes REST Sp1 synapsin I synapto-physin. Synaptophysin