After this fact was established, a number of scientists around the country began looking for the specific genes and proteins that could stabilize long-term memory.
One such signal had already been discovered by other scientists when they began their work -- the protein CREB. CREB is what is known as a transcription factor, a protein that interacts with the DNA of a gene and controls the early steps in "turning on" the expression of a new protein. Mutations in CREB prevent the activation of certain genes, and animals with defective forms of CREB have problems forming long-term memories.
But, scientists asked, was CREB the only protein that controls memory formation?
A few years ago, Korzus and Mayford were working at the UCSD School of Medicine, where in a collaboration with Michael G. Rosenfeld, M.D., who is a Howard Hughes Medical Institute Investigator and Professor of Medicine at UCSD, they began looking for other signals in neurons that affected the formation of long-term memory. Korzus and Mayford continued their work at Scripps Research, focusing on a mutation in rodents that affected a protein associated with CREB called CREB binding protein (CBP). CBP is what is known as a coactivator of transcription -- it works with CREB to control the expression of genes.
CBP is sort of like a molecular haberdasher. It grooms proteins involved in gene expression by fitting them with chemicals that turn them on or off. Specifically, CBP attaches acetyl groups to other proteins, and these acetyl accoutrements modulate their behavior in the cell.
One of the proteins in neurons that CBP acetylates are histones. Histones are short cylindrical proteins that associate with DNA in the nuclei of cells.
Histones are the fashion mavens of the molecular world. They must be wearing something! Normally, they have an affinity for wrapping themselves with DNA, and so DNA wraps around them in the cell, forming a compact bundle
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Contact: Jason Bardi
jasonb@scripps.edu
858-784-9254
Scripps Research Institute
23-Jun-2004