Transcription Factor Sp1 Is Essential for Early Embryonic Development but Dispensable for Cell Growth and Differentiation

Abstract

Transcription factor Sp1 has been implicated in the expression of many genes. Moreover, it has been suggested that Sp1 is linked to the maintenance of methylation-free CpG islands, the cell cycle, and the formation of active chromatin structures. We have inactivated the mouse Sp1 gene. Sp1-/- embryos are retarded in development, show a broad range of abnormalities, and die around day 11 of gestation. In Sp1-/- embryos, the expression of many putative target genes, including cell cycle-regulated genes, is not affected, CpG islands remain methylation free, and active chromatin is formed at the globin loci. However, the expression of the methyl-CpG-binding protein MeCP2 is greatly reduced in Sp1-/- embryos. MeCP2 is thought to be required for the maintenance of differentiated cells. We suggest that Sp1 is an important regulator of this process.

Functional analysis of two Sp1/Sp3 binding sites in murine Nanog gene promoter

“…Here we report that they are also involved in murine Nanog gene transcriptional regulation. However, Sp1 or Sp3 knockout mice were still able to form intact inner cell mass [13,14], suggesting that Sp1 and Sp3 have redundant functions that compensate for each other in Sp1 or Sp3 knockout mice, Perhaps the generation of ES cells with double knockout of Sp1 and Sp3 will unravel the question. …”

Overexpression of Sp1 transcription factor induces apoptosis

“…Sp1 deficiency causes a cell autonomous defect as when injected into wild-type blastocysts, Sp1-deficient embryonic stem cells contribute to every tissue of chimeras but only until day 10. These results suggest that Sp1 is required for cell survival and/or proliferation (Marin et al, 1997). Accordingly, sustained expression of Sp1 protects primary cortical neurons from cell death induced by oxidative stress or DNA damage (Ryu et al, 2003b).…”

“…The promoters of many antiapoptotic genes (bcl-2, bcl-x, survivin) as well as many proapoptotic genes (bax, trail, fas, fas-ligand, caspase-8 and caspase-3) contain Sp1-binding sites (Black et al, 2001). Although embryonic stem cells with inactivated Sp1 are viable, and grow and differentiate normally, Sp1 deficient embryos are retarded in development and die after day 10 of gestation (Marin et al, 1997). Sp1 deficiency causes a cell autonomous defect as when injected into wild-type blastocysts, Sp1-deficient embryonic stem cells contribute to every tissue of chimeras but only until day 10.…”

Reduced expression of the Sp4 gene in mice causes deficits in sensorimotor gating and memory associated with hippocampal vacuolization

“…Molecular Psychiatry ( Keywords: transcription factor; hippocampus; schizophrenia; mouse model; behavior; Cre recombinase; genetic rescue Sp1, the prototypal member of the Sp family of transcription factors, has been demonstrated to be essential for embryogenesis. 1 The reduction of its expression in heterozygous Sp1 mice causes a decreased expression of its downstream target gene, MeCP2, whose mutation is responsible for Rett syndrome, a human neurodevelopmental disorder. 2 Recently, Sp1 and other glutamine-rich transcription factors have been implicated in the pathogenesis of neurodegenerative diseases.…”