Work

Correction: Stem Cell Factor SALL4 Represses the Transcriptions of PTEN and SALL1 through an Epigenetic Repressor Complex

Year: 2009

Type: erratum

Abstract: Background: The embryonic stem cell (ESC) factor, SALL4, plays an essential role in both development and leukemogenesis.It is a unique gene that is involved in self-renewal in ESC and leukemic stem cell (LSC). Methodology/Principal Findings:To understand the mechanism(s) of SALL4 function(s), we sought to identify SALL4associated proteins by tandem mass spectrometry.Components of a transcription repressor Mi-2/Nucleosome Remodeling and Deacetylase (NuRD) complex were found in the SALL4-immunocomplexes with histone deacetylase (HDAC) activity in ESCs with endogenous SALL4 expression and 293T cells overexpressing SALL4.The SALL4-mediated transcriptional regulation was tested on two potential target genes: PTEN and SALL1.Both genes were confirmed as SALL4 downstream targets by chromatin-immunoprecipitation, and their expression levels, when tested by quantitative reverse transcription polymerase chain reaction (qRT-PCR), were decreased in 293T cells overexpressing SALL4.Moreover, SALL4 binding sites at the promoter regions of PTEN and SALL1 were co-occupied by NuRD components, suggesting that SALL4 represses the transcriptions of PTEN and SALL1 through its interactions with the Mi-2/NuRD complex.The in vivo repressive effect(s) of SALL4 were evaluated in SALL4 transgenic mice, where decreased expressions of PTEN and SALL1 were associated with myeloid leukemia and cystic kidneys, respectively.Conclusions/Significance: In summary, we are the first to demonstrate that stem cell protein SALL4 represses its target genes, PTEN and SALL1, through the epigenetic repressor Mi-2/NuRD complex.Our novel finding provides insight into the mechanism(s) of SALL4 functions in kidney development and leukemogenesis.

Source: PLoS ONE

DOI: 10.1371/annotation/e0bd3a57-1ce4-4eaf-83de-034d39cac787