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Publication : Involvement of histone demethylase LSD1 in Blimp-1-mediated gene repression during plasma cell differentiation.

First Author  Su ST Year  2009
Journal  Mol Cell Biol Volume  29
Issue  6 Pages  1421-31
PubMed ID  19124609 Mgi Jnum  J:145710
Mgi Id  MGI:3835879 Doi  10.1128/MCB.01158-08
Citation  Su ST, et al. (2009) Involvement of histone demethylase LSD1 in Blimp-1-mediated gene repression during plasma cell differentiation. Mol Cell Biol 29(6):1421-31
abstractText  Plasma cell differentiation is orchestrated by the transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1), which silences the gene expression program of mature B cells. The molecular mechanism underlying Blimp-1 suppression of mature B-cell gene expression is not fully understood. Here we report that a proline-rich domain in Blimp-1 directly interacts with LSD1, a histone lysine demethylase. Both LSD1 knockdown and expression of Blimp-1 lacking the proline-rich domain derepressed the activities of Blimp-1-dependent luciferase reporters. Disruption of the Blimp-1 interaction with LSD1 or reduced LSD1 expression attenuated antibody production, demonstrating the biological significance of this interaction. Finally, using chromatin immunoprecipitation, we showed that Blimp-1 binding to its target sites is accompanied by LSD1 binding to those same sites and that LSD1 binding correlates with histone modifications of accessible chromatin. These findings provide further insights into the molecular mechanism of the silencing of mature B-cell genes by Blimp-1 in plasma cell differentiation.
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