近日,，來自羅耀拉大學的研究者利用果蠅的基因開發(fā)出了一種新型的治療癌癥的武器,。研究者發(fā)現(xiàn)果蠅的某些基因和人類兩個癌癥發(fā)育相關的基因具有一定的相似性。隨著果蠅的基因不斷變化,，原先的一個基因變?yōu)閮蓚€,，這對于我們研究其功能提供了便利，這將對于研發(fā)抗癌新藥提供幫助,。相關研究成果刊登在了國際雜志Development上,。
正常細胞發(fā)育的過程中可以分裂為許多特殊類型的細胞，比如骨細胞和肌肉細胞等,，這個分類過程是受基因和激素互相協(xié)同調節(jié)的,，這些基因中的兩個為MLL1和MLL2。相反癌癥細胞的分裂卻不受控制,。
從2010年開始,，研究者發(fā)現(xiàn)一些癌癥，如非霍奇金淋巴瘤,、結直腸癌等癌癥和基因MLL2,、MLL3的突變相關，而且也有證據(jù)顯示,，這兩個基因的突變和乳腺癌,、前列腺癌相關。這兩個基因非常相似,，類似于彼此,，每一個基因均有15，000個堿基對,，是標準基因中堿基對數(shù)量的10倍以上,。因為這兩個基因如此的復雜，因此對于研究者研究來說有一定難度,。
在果蠅中,，相似基因MLL1和MLL2可以分裂為兩個基因TRR和CMI，每一個攜帶有正?；虻恼{節(jié)信息,。對果蠅中相似基因的分析使得我們可以更深入地對人類基因MLL1和MLL2進行研究分析。研究者Dingwall通過誘導果蠅中相似基因的突變,、檢測其突變后效應來研究基因的功能,，這將為我們理解MLL1和MLL2突變可以誘發(fā)癌癥細胞的無限制生長提供了基礎。
這項研究由美國國家科學基金會等機構給予資助,。（生物谷Bioon.com）
編譯自：Quirky Fruit Fly Gene Could Point Way to New Cancer Drugs
編譯者：天使托
doi:10.1242/dev.076687
PMC:
PMID:
Histone recognition and nuclear receptor co-activator functions of Drosophila Cara Mitad, a homolog of the N-terminal portion of mammalian MLL2 and MLL3
Chhavi Chauhan1,*, Claudia B. Zraly1,*,‡, Megan Parilla1, Manuel O. Diaz1,2 and Andrew K. Dingwall1,3,‡
MLL2 and MLL3 histone lysine methyltransferases are conserved components of COMPASS-like co-activator complexes. In vertebrates, the paralogous MLL2 and MLL3 contain multiple domains required for epigenetic reading and writing of the histone code involved in hormone-stimulated gene programming, including receptor-binding motifs, SET methyltransferase, HMG and PHD domains. The genes encoding MLL2 and MLL3 arose from a common ancestor. Phylogenetic analyses reveal that the ancestral gene underwent a fission event in some Brachycera dipterans, including Drosophila species, creating two independent genes corresponding to the N- and C-terminal portions. In Drosophila, the C-terminal SET domain is encoded by trithorax-related (trr), which is required for hormone-dependent gene activation. We identified the cara mitad (cmi) gene, which encodes the previously undiscovered N-terminal region consisting of PHD and HMG domains and receptor-binding motifs. The cmi gene is essential and its functions are dosage sensitive. CMI associates with TRR, as well as the EcR-USP receptor, and is required for hormone-dependent transcription. Unexpectedly, although the CMI and MLL2 PHDf3 domains could bind histone H3, neither showed preference for trimethylated lysine 4. Genetic tests reveal that cmi is required for proper global trimethylation of H3K4 and that hormone-stimulated transcription requires chromatin binding by CMI, methylation of H3K4 by TRR and demethylation of H3K27 by the demethylase UTX. The evolutionary split of MLL2 into two distinct genes in Drosophila provides important insight into distinct epigenetic functions of conserved readers and writers of the histone code.
