近日，nature杂志在线发表了耶鲁大学研究人员的研究成果，研究人员研究了转录因子中氨基酸取代对基因调控的影响。
基因组cis-调控区域中的变化在基因调控的演化中起重要作用。Lynch等人研究了转录因子中的氨基酸取代对基因调控的影响。他们发现了在演化过程中，“干系”胎生哺乳动物的转录因子CEBPB中的氨基酸取代是怎样重组关键磷酸化点的位置、从而改变它对cAMP/PKA信号作用的反应方式的。（生物谷Bioon.com）
doi:10.1038/nature10595
PMC:
PMID:
Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB
Vincent J. Lynch, Gemma May & Günter P. Wagner
There is an emerging consensus that gene regulation evolves through changes in cis-regulatory elements1, 2 and transcription factors3, 4, 5, 6. 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 regulation4, 5, 6, 7, 8, 9, 10. 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-3β-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.
