Protein arginine methyltransferase 6 controls erythroid gene expression and differentiation of human CD34(+) progenitor cells.
Protein arginine methyltransferase 6 controls erythroid gene expression and differentiation of human CD34(+) progenitor cells.
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蛋白精氨酸甲基转移酶6控制人CD34（+）祖细胞的红细胞基因表达和分化。
DOI：
10.3324/haematol.2017.174516
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发表时间：
2018-01
期刊：
影响因子：
10.1
通讯作者：
Lausen J
中科院分区：
文献类型：
--
作者：
Herkt SC;Kuvardina ON;Herglotz J;Schneider L;Meyer A;Pommerenke C;Salinas-Riester G;Seifried E;Bonig H;Lausen J
造血分化是由转录因子驱动的，转录因子协调着一个微调的转录网络。在双潜能分支点做出谱系决定，在那里关键的转录因子启动细胞类型特定的基因表达程序。这些程序由招募的染色质修饰辅因子的表观遗传活性稳定。一个例子是转录因子RUNX1与蛋白质精氨酸甲基转移酶6(PRMT6)在巨核/红系分叉处的关联。然而，关于PRMT6对这一重要分支点的具体影响还知之甚少。在这里，我们展示了PRMT6在原代人类CD34+祖细胞的巨核生成过程中抑制红系基因的表达。PRMT6被招募到血糖素A等红系基因中，从而建立了高H3R2me2a和低H3K4me3的抑制性组蛋白修饰模式。重要的是，用shRNA或小分子抑制剂抑制PRMT6会导致红系基因上调，促进红细胞生成。我们的数据显示，PRMT6在控制红系/巨核细胞分化中发挥作用，并为操纵PRMT6活性有助于促进红细胞生成用于治疗提供了可能性。
Hematopoietic differentiation is driven by transcription factors, which orchestrate a finely tuned transcriptional network. At bipotential branching points lineage decisions are made, where key transcription factors initiate cell type-specific gene expression programs. These programs are stabilized by the epigenetic activity of recruited chromatin-modifying cofactors. An example is the association of the transcription factor RUNX1 with protein arginine methyltransferase 6 (PRMT6) at the megakaryocytic/erythroid bifurcation. However, little is known about the specific influence of PRMT6 on this important branching point. Here, we show that PRMT6 inhibits erythroid gene expression during megakaryopoiesis of primary human CD34+ progenitor cells. PRMT6 is recruited to erythroid genes, such as glycophorin A. Consequently, a repressive histone modification pattern with high H3R2me2a and low H3K4me3 is established. Importantly, inhibition of PRMT6 by shRNA or small molecule inhibitors leads to upregulation of erythroid genes and promotes erythropoiesis. Our data reveal that PRMT6 plays a role in the control of erythroid/megakaryocytic differentiation and open up the possibility that manipulation of PRMT6 activity could facilitate enhanced erythropoiesis for therapeutic use.
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影响因子：
11.8
作者：
Goode DK;Obier N;Vijayabaskar MS;Lie-A-Ling M;Lilly AJ;Hannah R;Lichtinger M;Batta K;Florkowska M;Patel R;Challinor M;Wallace K;Gilmour J;Assi SA;Cauchy P;Hoogenkamp M;Westhead DR;Lacaud G;Kouskoff V;Göttgens B;Bonifer C
通讯作者：
Bonifer C
影响因子：
20.3
作者：
Ebert, BL;Lee, MM;Sieff, CA
通讯作者：
Sieff, CA
影响因子：
8
作者：
Cantor, AB;Orkin, SH
通讯作者：
Orkin, SH
影响因子：
64.5
作者：
Goldberg, Aaron D.;Allis, C. David;Bernstein, Emily
通讯作者：
Bernstein, Emily
DOI：
10.1073/pnas.0711961105
发表时间：
2008-04-22
影响因子：
11.1
作者：
Feng, Ru;Desbordes, Sabrina C.;Graf, Thomas
通讯作者：
Graf, Thomas