Method to enhance the transcription regulation of SUPT4H on genes containing repetitive nucleotide sequences

Abstract

Provided is a method of modulating the expression of a gene containing expanded nucleotide repeats in a cell, comprising: inhibiting the biological activity of SPT4 or SUPT4H; and regulating the formation of R-loops. The inhibition step can effectively reduce the expression of the gene containing the expanded nucleotide repeats and the regulatory step can further enhance the inhibition step. The inhibition step and the regulation step are for the purpose of regulating gene expression by interfering the capacity of RNA polymerase II transcribing over a DNA template with lengthy nucleotide repeats.

Description

technical field [0001] The non-provisional application claiming priority was filed in the United States on January 22, 2018 under 35 U.S.C. § 119(a) of the United States Patent Code under Patent No(s).(62 / 620,308), the patents listed above All the reference documents are cited as the disclosure content of this specification. Background technique [0002] Nucleotide repeat expansion diseases include a group of hereditary disorders caused by the instability and expansion of simple tandem repeats, usually trinucleotide repeats. Pathogenic nucleotide repeat expansions can occur in genes In diseases such as Friedreich's Ataxia, in coding or non-coding sequences, the expansion of non-coding sequences leads to silencing or downregulation of gene transcription, resulting in loss of gene function, so it is recessive inheritance. In contrast, in the condition of Huntington's disease, a CAG trinucleotide expansion occurs in the coding sequence of the gene, so that the resulting protei...

AI Technical Summary

Problems solved by technology

Trinucleotide repeat expansions can occur in the coding sequence or introns of a gene, and disease occurs when the number of nucleotide repeats exceeds a normal, stable threshold, and the number of repeats required for each gene to produce disease Slightly different; if the trinucleotide repeat expansion is present in the coding sequence of the gene, the mutation may result in a defective gene, and if the trinucleotide repeat expansion is present in an intron, it may form an RNA focus in the nucleus, cause toxic effects

However, the molecular mechanism of why SPT4 / SUPT4H assistance is required through highly repetitive nucleotide sequences during transcription elongation remains unclear.

Images