Histone lysine-specific demethylase 1 (LSD1) protein is involved in sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells

Li Liu, Joseph Souto, Wenbin Liao, Yongping Jiang, Yangqiu Li, Ryuichi Nishinakamura, Suming Huang, Todd Rosengart, Vincent W. Yang, Michael Schuster, Yupo Ma, Jianchang Yang

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18 Scopus citations

Abstract

The stem cell protein SALL4 plays a critical role in hematopoiesis by regulating the cell fate. In primitive hematopoietic precursors, it activates or represses important genes via recruitment of various epigenetic factors such as DNA methyltransferases, and histone deacylases. Here, we demonstrate that LSD1, a histone lysine demethylase, also participates in the trans-repressive effects of SALL4. Based on luciferase assays, the amine oxidase domain of LSD1 is important in suppressing SALL4-mediated reporter transcription. In freshly isolated adult mouse bone marrows, both SALL4 and LSD1 proteins are preferentially expressed in undifferentiated progenitor cells and co-localize in the nuclei. Further sequential chromatin immunoprecipitation assay confirmed that these two factors share the same binding sites at the promoter regions of important hematopoietic regulatory genes including EBF1, GATA1, and TNF. In addition, studies from both gain- and loss-of-function models revealed that SALL4 dynamically controls the binding levels of LSD1, which is accompanied by a reversely changed histone 3 dimethylated lysine 4 at the same promoter regions. Finally, shRNA-mediated knockdown of LSD1 in hematopoietic precursor cells resulted in altered SALL4 downstream gene expression and increased cellular activity. Thus, our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation.

Original languageEnglish (US)
Pages (from-to)34719-34728
Number of pages10
JournalJournal of Biological Chemistry
Volume288
Issue number48
DOIs
StatePublished - Nov 29 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Liu, L., Souto, J., Liao, W., Jiang, Y., Li, Y., Nishinakamura, R., Huang, S., Rosengart, T., Yang, V. W., Schuster, M., Ma, Y., & Yang, J. (2013). Histone lysine-specific demethylase 1 (LSD1) protein is involved in sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells. Journal of Biological Chemistry, 288(48), 34719-34728. https://doi.org/10.1074/jbc.M113.506568