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PBAF lacking PHD domains maintains transcription in human neutrophils.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2019-08-06 , DOI: 10.1016/j.bbamcr.2019.118525
Galina M Viryasova 1 , Victor V Tatarskiy 2 , Andrey A Sheynov 3 , Eugene V Tatarskiy 3 , Galina F Sud'ina 4 , Sofia G Georgieva 3 , Nataliya V Soshnikova 3
Affiliation  

The myeloid precursor cell differentiation requires an extensive chromatin remodeling. We show that the level of the PBAF chromatin remodeling complex decreases following the start of differentiation of myeloid precursors, becoming very low in the terminally differentiated peripheral blood (PB) neutrophils where it co-localizes with Pol II on the transcriptionally active chromatin. Previously, we have shown that the PHF10 subunit of the PBAF signature module has four isoforms, two of them (PHF10-P) contain a tandem of C-terminal PHD domains. We found that out of four PHF10 isoforms present in the myeloid precursor cells, only the PHF10-Ss isoform lacking PHD domains, is actively expressed in the PB neutrophils. In particular, the longest of the PHF10 isoforms (PHF10-Pl), which is essential for proliferation, completely disappears in PB neutrophils. In addition, in the myeloid precursors, promoters of neutrophil-specific genes are associated with the PHD-containing isoforms, together with PBAF and Pol II, when these genes are inactive and only during their activation stage. However, at the later stages of differentiation, when neutrophil-specific genes are actively transcribed, PHF10-P isoforms on their promoters are replaced by the PHF10-S isoforms. Evidently, PHD domains of PHF10 are essential for active chromatin remodeling during transcription activation, but are dispensable for the constantly transcribed genes.

中文翻译:

缺乏PHD结构域的PBAF在人类嗜中性粒细胞中维持转录。

髓样前体细胞分化需要广泛的染色质重塑。我们表明,PBAF染色质重塑复合体的水平随着髓样前体的分化开始而降低,在终末分化外周血(PB)中性粒细胞中非常低,在该水平中它与Pol II共同位于转录活性染色质上。以前,我们已经证明PBAF签名模块的PHF10亚基具有四个同工型,其中两个(PHF10-P)包含串联的C末端PHD域。我们发现,在髓样前体细胞中存在的四种PHF10亚型中,只有缺乏PHD结构域的PHF10-Ss亚型在PB中性粒细胞中活跃表达。特别地,对于增殖必不可少的最长的PHF10同工型(PHF10-P1)在PB中性粒细胞中完全消失。另外,在髓样前体中,中性粒细胞特异性基因的启动子与含PHD的同工型以及PBAF和Pol II结合在一起,此时这些基因是无活性的并且仅在它们的激活阶段。但是,在分化的后期,当嗜中性粒细胞特异性基因被主动转录时,其启动子上的PHF10-P亚型被PHF10-S亚型替代。显然,PHF10的PHD域对于转录激活过程中的活性染色质重塑是必不可少的,但对于不断转录的基因却是必不可少的。当嗜中性粒细胞特异性基因被主动转录时,其启动子上的PHF10-P亚型被PHF10-S亚型替代。显然,PHF10的PHD域对于转录激活过程中的活性染色质重塑是必不可少的,但对于不断转录的基因却是必不可少的。当嗜中性粒细胞特异性基因被主动转录时,其启动子上的PHF10-P亚型被PHF10-S亚型替代。显然,PHF10的PHD域对于转录激活过程中的活性染色质重塑是必不可少的,但对于不断转录的基因却是必不可少的。
更新日期:2019-08-06
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