Demers Celina, Chaturvedi Chandra-Prakash, Ranish Jeffrey A, Juban Gaetan, Lai Patrick, Morle Francois, Aebersold Ruedi, Dilworth F Jeffrey, Groudine Mark, Brand Marjorie
Sprott Center for Stem Cell Research, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
Mol Cell. 2007 Aug 17;27(4):573-84. doi: 10.1016/j.molcel.2007.06.022.
MLL-containing complexes methylate histone H3 at lysine 4 (H3K4) and have been implicated in the regulation of transcription. However, it is unclear how MLL complexes are targeted to specific gene loci. Here, we show that the MLL2 complex associates with the hematopoietic activator NF-E2 in erythroid cells and is important for H3K4 trimethylation and maximal levels of transcription at the beta-globin locus. Furthermore, recruitment of the MLL2 complex to the beta-globin locus is dependent upon NF-E2 and coincides spatio-temporally with NF-E2 binding during erythroid differentiation. Thus, a DNA-bound activator is important initially for guiding MLL2 to a particular genomic location. Interestingly, while the MLL2-associated subunit ASH2L is restricted to the beta-globin locus control region 38 kb upstream of the beta(maj)-globin gene, the MLL2 protein spreads across the beta-globin locus, suggesting a previously undefined mechanism by which an activator influences transcription and H3K4 trimethylation at a distance.
含MLL的复合物使组蛋白H3的赖氨酸4位点（H3K4）发生甲基化，并参与转录调控。然而，目前尚不清楚MLL复合物是如何靶向特定基因位点的。在此，我们发现MLL2复合物在红细胞中与造血激活因子NF-E2结合，对β-珠蛋白基因座处的H3K4三甲基化和最大转录水平至关重要。此外，MLL2复合物募集到β-珠蛋白基因座依赖于NF-E2，并且在红细胞分化过程中与NF-E2的结合在时空上相吻合。因此，一种与DNA结合的激活因子最初对于将MLL2引导至特定基因组位置很重要。有趣的是，虽然与MLL2相关的亚基ASH2L局限于β（maj）-珠蛋白基因上游38 kb的β-珠蛋白基因座控制区域，但MLL2蛋白却分布于整个β-珠蛋白基因座，这提示了一种此前未明确的机制，即激活因子可在远距离影响转录和H3K4三甲基化。
