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首页> 外文期刊>Journal of Cellular Physiology >Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes.
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Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required for myeloid differentiation to granulocytes.

机译：的atp酶亚基缺失,瑞士/ SNF染色质重构复杂,需要骨髓粒细胞的分化。

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摘要

Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic subunit to remodel nucleosomes for transcription regulation. In several mesenchymal cells and tissues, expression of a defective Brg1 protein negates the normal activity of the SWI/SNF complex and delays or blocks differentiation. To investigate the role of SWI/SNF complexes during myelopoiesis, we stably expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage. Forced expression of dnBrg1 in IL-3-dependent murine 32Dcl3 myeloid progenitor cells results in a profound delay in the granulocyte-colony stimulating factor (G-CSF) induced granulocytic maturation. These cells also exhibit a significant decrease in the expression of both CD11b and Gr-1 surface receptors, which are normally upregulated during granulopoiesis, and show sustained expression of myeloperoxidase, which is synthesized primarily during the promyelocytic (blast) stage of myeloid development. Thus, dnBrg1 expression causes a developmental block at the promyelocytic/metamyelocytic stage of myeloid differentiation. Our findings indicate that the normal chromatin remodeling function of Brg1 is necessary for the G-CSF dependent differentiation of myeloid cells towards the granulocytic lineage. This dependency on Brg1 may reflect a stringent requirement for chromatin remodeling at a critical stage of hematopoietic cell maturation.
机译：许多哺乳动物使用瑞士/ SNF复合物作为催化Brahma-related基因1(缺失)对转录单元改造核小体监管。组织,表达的蛋白质有缺陷的缺失否定瑞士/ SNF的正常活动复杂的和延迟或块分化。调查期间瑞士/ SNF复合物的作用骨髓形成,我们稳定表达了占主导地位的负(dn)骨髓血统的缺失突变体。迫使IL-3-dependent dnBrg1的表达式鼠32 dcl3骨髓祖细胞的结果粒细胞集落的延迟引起粒细胞刺激因子(g - csf)成熟。的表达明显下降CD11b和Gr-1表面受体通常在粒细胞生成调节,显示持续的髓过氧物酶的表达,合成过程中主要是哪一个早幼粒细胞(爆炸)阶段的骨髓发展。发展块早幼粒细胞/ metamyelocytic骨髓阶段分化。正常的染色质重塑功能缺失必要的g - csf依赖分化骨髓细胞粒细胞血统。严格要求染色质重塑造血细胞的关键阶段成熟。

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