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Identification of differential expressed genes after SP1 or SP3 knockdown in colorectal cancer cells

ABSTRACT: SP1 and SP3 have been reported to play an critical role in the pregression of tumors. In order to elucidate the molecular mechanism of SP1 and SP3 in colorectal cancer, RNA-seq analysis was performed on SP1 and SP3 knockdown and control HCT116 cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE179314 | GEO | 2024/07/01

REPOSITORIES: GEO

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Identification of differential expressed genes after SP1 or SP3 knockdown in colorectal cancer cells

Project description:Identification of differential expressed genes after SP1 or SP3 knockdown in colorectal cancer cells

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Robust hematopoietic specification requires the ubiquitous Sp1 and Sp3 transcription factors

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

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

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Project description:Sp1 and Sp3 belong to the Specificity proteins (Sp)/Krüppel-like transcription factor family. They are closely related, ubiquitously expressed and recognize G-rich DNA motifs. They are thought to regulate generic processes such as cell cycle and growth control, metabolic pathways and apoptosis. Ablation of Sp1 or Sp3 in mice is lethal, and combined haploinsufficiency results in hematopoietic defects during the fetal stages. Here, we show that in adult mice conditional ablation of either Sp1 or Sp3 has minimal impact on hematopoiesis, while the simultaneous loss of Sp1 and Sp3 results in severe macrothrombocytopenia and platelet dysfunction. We employed flow cytometry, cell culture and electron microscopy and show that although megakaryocyte numbers are normal in bone marrow and spleen, they display a less compact demarcation membrane system and a striking inability to form proplatelets. Through megakaryocyte transcriptomics and platelet proteomics we identified several cytoskeleton-related proteins and downstream effector kinases, including Mylk, that were downregulated upon Sp1/Sp3 depletion, providing an explanation for the observed defects in megakaryopoiesis. We show that Mylk is required for proplatelet formation and stabilization and for ITAM-receptor mediated platelet aggregation. Our data highlights the specific vs generic role of these ubiquitous transcription factors in the highly specialized megakaryocytic lineage.

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Sp1/Sp3 transcription factors regulate hallmarks of megakaryocyte maturation, and platelet formation and function

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