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Requisite chromatin remodeling for myeloid and erythroid lineage differentiation from erythromyeloid progenitors

ABSTRACT: The mammalian 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 encoding a subunit of BAF complex in the Tie2(+) lineage (Baf155 CKO) leads to defects in the yolk sac myeloid and definitive erythroid (EryD) lineage differentiation from erythromyeloid progenitors (EMPs) and embryonic lethality. Baf155 knock-down in EMP was sufficient to block myeloid and EryD differentiation. Chromatin of the myeloid gene loci in Baf155 CKO EMPs was largely inaccessible and was enriched mostly by the ETS binding motif. BAF155 interacted with PU.1 and was recruited to the PU.1 in target gene loci together with p300 and KDM6a. Treatment of Baf155 CKO embryos with GSK126, an inhibitor of the H3K27me2/3 methyltransferase EZH2, rescued myeloid lineage gene expression. These studies uncover the indispensable BAF mediated chromatin remodeling of the myeloid gene loci at the EMP stage.

ORGANISM(S): Mus musculus

PROVIDER: GSE159381 | GEO | 2021/03/08

REPOSITORIES: GEO

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Requisite chromatin remodeling for myeloid and erythroid lineage differentiation from erythromyeloid progenitors

Project description:The mammalian SWI/SNF chromatin-remodeling BAF (BRG1/BRM-associated factor) complex has an essential role in developmental and pathological processes. We show that deletion of Baf155 encoding 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 generation and application of EMP derivatives for tissue repair, regeneration, and disease are warranted.

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