The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells.
The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells.
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DOI：
10.1002/stem.2604
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Stopka T
中科院分区：
文献类型：
--
作者：
Kokavec J;Zikmund T;Savvulidi F;Kulvait V;Edelmann W;Skoultchi AI;Stopka T
模拟开关核ATP酶Smarca 5（Snf 2 h）是最保守的染色质重塑因子之一。它存在于各种寡亚基复合物中，这些复合物相对于组蛋白八聚体移动DNA以产生规则间隔的核小体阵列。Smarca 5与不同的辅助蛋白相互作用，代表DNA复制，修复和转录的分子马达。我们在确定性造血（Vav 1-iCre）开始时删除Smarca 5，并观察到动物在胎儿发育后期因贫血而死亡。造血干细胞和祖细胞的积累，但他们向红系和髓系的成熟受到抑制。原成红细胞发育不良，而嗜碱性成红细胞阻滞在G2/M期并耗竭。Smarca 5缺陷导致p53水平增加，其在两个残基处活化，一个与DNA损伤（S15 Phos）相关，第二个与CBP/p300（K376 Ac）相关，最后活化p53靶标。我们还删除了定向红系细胞（Epor-iCre）中的Smarca 5，并观察到动物出生后贫血。此外，在离体培养物中4-羟基他莫昔芬介导的Smarca 5缺失证实了其对红系细胞增殖的需要。因此，Smarca 5在早期造血和红细胞生成中起着不可或缺的作用。
The imitation switch nuclear ATPase Smarca5 (Snf2h) is one of the most conserved chromatin remodeling factors. It exists in a variety of oligosubunit complexes that move DNA with respect to the histone octamer to generate regularly spaced nucleosomal arrays. Smarca5 interacts with different accessory proteins and represents a molecular motor for DNA replication, repair, and transcription. We deleted Smarca5 at the onset of definitive hematopoiesis (Vav1-iCre) and observed that animals die during late fetal development due to anemia. Hematopoietic stem and progenitor cells accumulated but their maturation toward erythroid and myeloid lineages was inhibited. Proerythroblasts were dysplastic while basophilic erythroblasts were blocked in G2/M and depleted. Smarca5 deficiency led to increased p53 levels, its activation at two residues, one associated with DNA damage (S15Phos) second with CBP/p300 (K376Ac), and finally activation of the p53 targets. We also deleted Smarca5 in committed erythroid cells (Epor-iCre) and observed that animals were anemic postnatally. Furthermore, 4-hydroxytamoxifen-mediated deletion of Smarca5 in the ex vivo cultures confirmed its requirement for erythroid cell proliferation. Thus, Smarca5 plays indispensable roles during early hematopoiesis and erythropoiesis.
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影响因子：
16.6
作者：
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影响因子：
64.5
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通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
Kapur, R
DOI：
10.1073/pnas.90.13.5954
发表时间：
1993-07-01
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
20.3
作者：
Heinrich, AC;Pelanda, R;Klingmüller, U
通讯作者：
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