Transcriptional promoter for human BACE1 gene as well as main cis-acting elements and application of transcriptional promoter

Abstract

The invention provides a transcriptional promoter for the human BACE1 gene as well as a core promoter region and cis-acting elements of the transcriptional promoter. According to the invention, the smallest promoter region defining the high-level transcription of the human BACE1 gene and the core promoter region defining basal transcription of the human BACE1 gene are firstly confirmed, and the two cis-acting elements capable of enhancing gene transcription are confirmed, the structure of the BACE1 gene promoter core region playing a key function on the transcription of the BACE1 gene is disclosed, and a transcription regulatory mechanism of the BACE1 gene and influence, found through the transcription regulatory mechanism, on the transcription and expression of the BACE1 gene are understood more deeply. Effective action target spots are provided for preventing, diagnosing and treating AD and other diseases.

Description

technical field [0001] The invention relates to a human gene promoter and its main cis-acting element, in particular to the expression and regulation of human BACE1 gene. Background technique [0002] The BACE1 gene encodes β-site amyloid precursor protein cleavage enzyme (BACE1, also known as Asp2 or memapsin2), which is a transmembrane aspartic acid protease with 501 amino acids. BACE1 is the only β-secretase in the human body, which generates β-amyloid protein (amyloid β peptide, Aβ) by cleaving amyloid precursor protein (AβPP or APP), which is a rate-limiting step of Aβ production. In the brains of Alzheimer's disease (AD) patients, Aβ is an important pathological manifestation - the main component of amyloid neuritic plaques, and Aβ deposition plays a key role in the occurrence and development of AD. Reducing the generation of Aβ by inhibiting the activity of BACE1 has become the target of drug development for the prevention and treatment of AD. [0003] The human BAC...

AI Technical Summary

Problems solved by technology

The cis-acting elements bound by the above-mentioned many transcription factors are located far upstream from the transcription initiation site and play a regulatory role in transcription, and the transcription factors that combine with these cis-acting elements to play a transcriptional regulatory role depend on It plays a role in the interaction with general transcription factors. At present, there are few studies on the interaction between BACE1 gene and general transcription factors and the core promoter region located near the transcription start site. However, studies in recent years have shown that general Transcription factors are not only related to the basal expression of genes, but also to the specific expression of genes in time and space

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