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Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE126501 | GEO | 2019/06/06

REPOSITORIES: GEO

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Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors.

Project description:BackgroundBoth tissue-specific and ubiquitously expressed transcription factors, such as Sp-family members, are required for correct development. However, the molecular details of how ubiquitous factors are involved in programming tissue-specific chromatin and thus participate in developmental processes are still unclear. We previously showed that embryonic stem cells lacking Sp1 DNA-binding activity (Sp1ΔDBD/ΔDBD cells) are able to differentiate into early blood progenitors despite the inability of Sp1 to bind chromatin without its DNA-binding domain. However, gene expression during differentiation becomes progressively deregulated, and terminal differentiation is severely compromised.ResultsHere, we studied the cooperation of Sp1 with its closest paralogue Sp3 in hematopoietic development and demonstrate that Sp1 and Sp3 binding sites largely overlap. The complete absence of either Sp1 or Sp3 or the presence of the Sp1 DNA-binding mutant has only a minor effect on the pattern of distal accessible chromatin sites and their transcription factor binding motif content, suggesting that these mutations do not affect tissue-specific chromatin programming. Sp3 cooperates with Sp1ΔDBD/ΔDBD to enable hematopoiesis, but is unable to do so in the complete absence of Sp1. Using single-cell gene expression analysis, we show that the lack of Sp1 DNA binding leads to a distortion of cell fate decision timing, indicating that stable chromatin binding of Sp1 is required to maintain robust differentiation trajectories.ConclusionsOur findings highlight the essential contribution of ubiquitous factors such as Sp1 to blood cell development. In contrast to tissue-specific transcription factors which are required to direct specific cell fates, loss of Sp1 leads to a widespread deregulation in timing and coordination of differentiation trajectories during hematopoietic specification.

| S-EPMC6547542 | biostudies-literature

Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors

Project description:Development requires the cooperation of tissue-specifically and ubiquitously expressed transcription factors, such as Sp-family members. However, the molecular details of how ubiquitous factors participate in developmental processes are still unclear. We previously showed that during the differentiation of embryonic stem cells lacking Sp1 DNA binding activity (Sp1DDBD/DDBD cells), early blood progenitors are formed. However, gene expression during differentiation becomes progressively deregulated and terminal differentiation is blocked. Here we studied the cooperation of Sp1 and its homologue Sp3 in hematopoietic development and demonstrate that Sp1 and Sp3 binding sites largely overlap. Sp3 cooperates with Sp1DDBD/DDBD cells but is unable to support hematopoiesis in the complete absence of Sp1. Using single cell gene expression analysis, we show that the lack of Sp1 DNA binding leads to a distortion of cell fate decision timing, indicating that stable chromatin binding of Sp1 is required to maintain robust differentiation trajectories.

2019-06-04 | GSE126497 | GEO

Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors [RNA-seq]

Project description:Development requires the cooperation of tissue-specific and ubiquitously expressed transcription factors, such as Sp-family members. However, the molecular details of how ubiquitous factors participate in developmental processes are still unclear. We previously showed that during the differentiation of embryonic stem cells lacking Sp1 DNA binding activity (Sp1deltaDBD/deltaDBD cells), early blood progenitors are formed. However, gene expression during differentiation becomes progressively deregulated and terminal differentiation is severely compromised. Here we studied the cooperation of Sp1 and its closest paralogue Sp3 in hematopoietic development and demonstrate that Sp1 and Sp3 binding sites largely overlap. Sp3 cooperates with Sp1deltaDBD/deltaDBD but is unable to support hematopoiesis in the complete absence of Sp1. Using single cell gene expression analysis, we show that the lack of Sp1 DNA binding leads to a distortion of cell fate decision timing, indicating that stable chromatin bi nding of Sp1 is required to maintain robust differentiation trajectories.

2019-06-06 | GSE126500 | GEO

Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors [ChIP-seq]

2019-06-06 | GSE126496 | GEO

Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors [ATAC-Seq]

2019-06-06 | GSE126493 | GEO

Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors

Project description:Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors

| PRJNA522083 | ENA

Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors

Project description:Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors

| PRJNA522247 | ENA

Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors [ChIP-seq]