m**e
发帖数: 857 | 1 can you believe of it? Just 3 amino acid.
Regulatory evolution through divergence of a phosphoswitch in the
transcription factor CEBPB
Lynch VJ, May G, Wagner GP.
Nature. 2011 Nov 13;480(7377):383-6. doi: 10.1038/nature10595.
Abstract
There is an emerging consensus that gene regulation evolves through changes
in cis-regulatory elements and transcription factors. Although it is clear
how nucleotide substitutions in cis-regulatory elements affect gene
expression, it is not clear how amino-acid substitutions in transcription
factors influence gene regulation. Here we show that amino-acid changes in
the transcription factor CCAAT/enhancer binding protein-β (CEBPB, also
known as C/EBP-β) in the stem-lineage of placental mammals changed the way
it responds to cyclic AMP/protein kinase A (cAMP/PKA) signalling. By
functionally analysing resurrected ancestral proteins, we identify three
amino-acid substitutions in an internal regulatory domain of CEBPB that are
responsible for the novel function. These amino-acid substitutions
reorganize the location of key phosphorylation sites, introducing a new site
and removing two ancestral sites, reversing the response of CEBPB to GSK-3
β-mediated phosphorylation from repression to activation. We conclude that
changing the response of transcription factors to signalling pathways can be
an important mechanism of gene regulatory evolution. |
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