Requisite Chromatin Remodeling for Myeloid and Erythroid Lineage Differentiation from Erythromyeloid Progenitors.
Requisite Chromatin Remodeling for Myeloid and Erythroid Lineage Differentiation from Erythromyeloid Progenitors.
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从红髓系祖细胞分化髓系和红系所需的染色质重塑。
DOI：
10.1016/j.celrep.2020.108395
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发表时间：
2020-11-17
期刊：
影响因子：
8.8
通讯作者：
Choi K
中科院分区：
文献类型：
--
作者：
Wu J;Krchma K;Lee HJ;Prabhakar S;Wang X;Zhao H;Xing X;Seong RH;Fremont DH;Artyomov MN;Wang T;Choi K
哺乳动物开关/蔗糖不可发酵（SWI/SNF）染色质重塑BAF （BRG1/ brm相关因子）复合物在发育和病理过程中发挥重要作用。我们发现，在Tie2（+）谱系中，编码BAF复合物亚基的Baf155 （CKO）的缺失会导致卵黄囊髓系和终性红细胞（EryD）谱系从红髓系祖细胞（EMPs）分化的缺陷。Baf155 CKO EMPs中髓系基因位点的染色质大部分是不可接近的，主要由ETS结合基序富集。BAF155与PU.1相互作用，并与p300和KDM6a一起被募集到PU.1靶基因位点。用H3K27me2/3甲基转移酶EZH2抑制剂GSK126处理Baf155 CKO胚胎，可挽救髓系基因表达。本研究揭示了在EMP阶段髓系基因位点不可缺少的baf介导的染色质重塑。未来的研究需要利用表观遗传学来产生和应用EMP衍生物用于组织修复、再生和疾病。哺乳动物染色质重塑BAF （BRG1/ brm相关因子）复合物在发育和病理过程中起重要作用。Wu等人表明，在EMP阶段，baf介导的染色质重塑和髓系和终系红系转录程序的激活对髓系和终系红系的发育至关重要。
The mammalian SWitch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling BAF (BRG1/BRM-associated factor) complex plays an essential role in developmental and pathological processes. We show that the deletion of Baf155, which encodes a subunit of the BAF complex, in the Tie2(+) lineage (Baf155 (CKO) leads to defects in yolk sac myeloid and definitive erythroid (EryD) lineage differentiation from erythromyeloid progenitors (EMPs). The chromatin of myeloid gene loci in Baf155 CKO EMPs is mostly inaccessible and enriched mainly by the ETS binding motif. BAF155 interacts with PU.1 and is recruited to PU.1 target gene loci together with p300 and KDM6a. Treatment of Baf155 CKO embryos with GSK126, an H3K27me2/3 methyltransferase EZH2 inhibitor, rescues myeloid lineage gene expression. This study uncovers indispensable BAF-mediated chromatin remodeling of myeloid gene loci at the EMP stage. Future studies exploiting epigenetics in the generation and application of EMP derivatives for tissue repair, regeneration, and disease are warranted. The mammalian chromatin-remodeling BAF (BRG1/BRM-associated factor) complex has an essential role in developmental and pathological processes. Wu et al. show that BAF-mediated chromatin remodeling and activation of the myeloid and definitive erythroid transcriptional program at the EMP stage is critical for myeloid and definitive erythroid lineage development.
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影响因子：
7.7
作者：
Azzoni E;Frontera V;McGrath KE;Harman J;Carrelha J;Nerlov C;Palis J;Jacobsen SEW;de Bruijn MF
通讯作者：
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48
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作者：
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16
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