Bausero P, Schmitt M, Toussaint J L, Simoni P, Geoffroy V, Queuche D, Duclaud S, Kempf J, Quirin-Stricker C
Institut de Chimie Biologique de la Faculté de Médecine, Strasbourg, France.
Neuroreport. 1993 Mar;4(3):287-90. doi: 10.1097/00001756-199303000-00015.
Choline acetyltransferase (ChAT) is the key enzyme responsible for the synthesis of the neurotransmitter acetylcholine and is reduced in various central neurodegenerative diseases. From a previously selected 12.6 kb human choline acetyltransferase (hChAT) genomic clone, we have identified and characterized a promoter region of 895 bp. Sequence analysis revealed the presence of a TATA-like box, a CAAT box and several putative regulatory responsive elements. Three transcription initiation sites were determined by primer extension analysis. The Northern blot of poly(A)+ RNA, showed a single band of 2300 Nt in the human nucleus accumbens and facial nucleus. By using transient transfections into NE-1-115 and COS-1 cells of the 5' flanking region of the hChAT gene we identified a sequence of 66 bp upstream of the transcription start site which confers responsiveness to proto-oncogenes c-Fos/c-Jun. These data suggest that the hChAT gene may be a physiological target of c-Fos/c-Jun and therefore may play a role in neuronal responses to various stimuli.
胆碱乙酰转移酶（ChAT）是负责合成神经递质乙酰胆碱的关键酶，在各种中枢神经退行性疾病中含量会降低。从先前选定的12.6 kb人类胆碱乙酰转移酶（hChAT）基因组克隆中，我们鉴定并表征了一个895 bp的启动子区域。序列分析揭示了一个类TATA盒、一个CAAT盒以及几个推定的调控反应元件的存在。通过引物延伸分析确定了三个转录起始位点。聚腺苷酸加尾RNA（poly(A)+ RNA）的Northern印迹显示，在人伏隔核和面神经核中有一条2300个核苷酸的单带。通过将hChAT基因5'侧翼区域瞬时转染到NE-1-115和COS-1细胞中，我们在转录起始位点上游66 bp处鉴定出一个序列，该序列赋予了对原癌基因c-Fos/c-Jun的反应性。这些数据表明，hChAT基因可能是c-Fos/c-Jun的生理靶点，因此可能在神经元对各种刺激的反应中发挥作用。
