Compositions and methods for treating alzheimer's disease utilizing a transcriptional master regulator of the retromer complex

A method for identifying the DNA-binding profile of a dimeric transcription factor complex in vivo, comprising:

• (a) generating a DNA construct of a first transcription factor comprising:
• (i) fusing a specific first dimerization domain to the C-terminal of the first transcription factor;
• and (ii) adding a first N-terminal epitope tag to the first transcription factor;
• (b) generating a DNA construct of a second transcription factor comprising:
• (i) fusing a specific second dimerization domain to the C-terminal of the second transcription factor, wherein the second dimerization domain is different from the first dimerization domain;
• and (ii) adding a second N-terminal epitope tag to the second transcription factor, wherein the second N-terminal epitope tag is different from the first N-terminal epitope tag;
• (c) identifying a bivalent ligand that recognizes both dimerization domains from steps (a) and (b);
• (d) co-transfecting a host cell with the DNA constructs generated in steps (a)-(b) and co-expressing polypeptides encoded by the DNA constructs in the presence of the bivalent ligand identified in step (c) to form the dimeric transcription factor complex;
• and
• (e) identifying the DNA-binding profile of the dimeric transcription factor complex by determining the complex's binding sites to the genome using ChIP-sequencing (ChIP-seq).