PBAF lacking PHD domains maintains transcription in human neutrophils

https://doi.org/10.1016/j.bbamcr.2019.118525Get rights and content
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Highlights

  • The level of PBAF chromatin-remodeling complex decreases during myelogenesis.

  • PBAF localizes in transcriptionally active chromatin in human neutrophils.

  • The isoforms of PHF10/BAF45a subunit of PBAF replace each other in PBAF complex during myeloid differentiation.

  • PHF10-P isoform present at myeloid genes promoters during activation but are replaced by PHF10-Ss during stable transcription.

Abstract

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.

Keywords

Myeloid differentiation
Neutrophils
Chromatin remodeling
PBAF complex
PHF10 isoforms
CD66 genes

Data availability statement

All data generated or analyzed during this study are included in this published article (and its Supplementary information file).

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