現(xiàn)在人們已經(jīng)接受了成年腦有生長新細(xì)胞的彈性這樣一個觀點(diǎn)，但在腦中某些區(qū)域一生中維持神經(jīng)生成的分子機(jī)制尚不清楚,。影響基因表達(dá)的一大因素是染色質(zhì)（核苷酸與構(gòu)成染色體的蛋白組成的復(fù)合物）的結(jié)構(gòu),。
現(xiàn)在,，Lim等人發(fā)現(xiàn)，在出生后小鼠的腦中,，染色質(zhì)重塑因子基因“Mll1 (mixed lineage leukaemia 1)”促使神經(jīng)干細(xì)胞形成神經(jīng)元,，而在沒有Mll1的情況下，同樣的干細(xì)胞則會產(chǎn)生神經(jīng)膠質(zhì)細(xì)胞,，它們是在神經(jīng)系統(tǒng)中主要起輔助作用的非神經(jīng)元細(xì)胞,。Mll1部分是通過激發(fā)下游基因Dlx2起作用的，后者是腦室下區(qū)（subventricular zone）中神經(jīng)生成的一個關(guān)鍵調(diào)控因子,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 458, 529-533 (26 March 2009) | doi:10.1038/nature07726
Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells
Daniel A. Lim1,2,3,8, Yin-Cheng Huang1,2,8,9, Tomek Swigut4, Anika L. Mirick5, Jose Manuel Garcia-Verdugo6,7, Joanna Wysocka4, Patricia Ernst5 & Arturo Alvarez-Buylla1,2
1 Department of Neurological Surgery,
2 Institute for Regeneration Medicine, and,
3 Veteran's Affairs Medical Center, University of California, San Francisco, 505 Parnassus Street M779, San Francisco, California 94143, USA
4 Department of Chemical and Systems Biology, Department of Developmental Biology Stanford University School of Medicine, Stanford, California 94305, USA
5 Department of Genetics, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
6 Laboratorio de Neurobiologia Comparada, Instituto Cavanilles, Universidad de Valencia, Valencia 46012, Spain
7 Laboratorio de Morfologia Celular, Centro de Investigación Príncipe Felipe, CIBERNED, Valencia 46012, Spain
8 These authors contributed equally to this work.
9 Present address: Department of Neurosurgery, Graduate Institute of Clinical Medical Science, ChangGung Univerisity, Kwei-Shan, Tao-yuan, Taiwan.
10 Correspondence to: Daniel A. Lim1,2,3,8Arturo Alvarez-Buylla1,2 Correspondence and requests for materials should be addressed to D.A.L.
Epigenetic mechanisms that maintain neurogenesis throughout adult life remain poorly understood1. Trithorax group (trxG) and Polycomb group (PcG) gene products are part of an evolutionarily conserved chromatin remodelling system that activate or silence gene expression, respectively2. Although PcG member Bmi1 has been shown to be required for postnatal neural stem cell self-renewal3, 4, the role of trxG genes remains unknown. Here we show that the trxG member Mll1 (mixed-lineage leukaemia 1) is required for neurogenesis in the mouse postnatal brain. Mll1-deficient subventricular zone neural stem cells survive, proliferate and efficiently differentiate into glial lineages; however, neuronal differentiation is severely impaired. In Mll1-deficient cells, early proneural Mash1 (also known as Ascl1) and gliogenic Olig2 expression are preserved, but Dlx2, a key downstream regulator of subventricular zone neurogenesis, is not expressed. Overexpression of Dlx2 can rescue neurogenesis in Mll1-deficient cells. Chromatin immunoprecipitation demonstrates that Dlx2 is a direct target of MLL in subventricular zone cells. In differentiating wild-type subventricular zone cells, Mash1, Olig2 and Dlx2 loci have high levels of histone 3 trimethylated at lysine 4 (H3K4me3), consistent with their transcription. In contrast, in Mll1-deficient subventricular zone cells, chromatin at Dlx2 is bivalently marked by both H3K4me3 and histone 3 trimethylated at lysine 27 (H3K27me3), and the Dlx2 gene fails to properly activate. These data support a model in which Mll1 is required to resolve key silenced bivalent loci in postnatal neural precursors to the actively transcribed state for the induction of neurogenesis, but not for gliogenesis.
