近日，nature雜志在線發(fā)表了耶魯大學(xué)研究人員的研究成果,，研究人員研究了轉(zhuǎn)錄因子中氨基酸取代對(duì)基因調(diào)控的影響。
基因組cis-調(diào)控區(qū)域中的變化在基因調(diào)控的演化中起重要作用,。Lynch等人研究了轉(zhuǎn)錄因子中的氨基酸取代對(duì)基因調(diào)控的影響,。他們發(fā)現(xiàn)了在演化過程中，“干系”胎生哺乳動(dòng)物的轉(zhuǎn)錄因子CEBPB中的氨基酸取代是怎樣重組關(guān)鍵磷酸化點(diǎn)的位置,、從而改變它對(duì)cAMP/PKA信號(hào)作用的反應(yīng)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.
