Involvement of histone demethylase LSD1 in Blimp-1-mediated gene repression during plasma cell differentiation.
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.
Su
Shin-Tang
ST
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Ying
Hsia-Yuan
HY
Chiu
Yi-Kai
YK
Lin
Fan-Ru
FR
Chen
Mei-Yu
MY
Lin
Kuo-I
KI
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D020868:Gene Silencing; D056466:Histone Demethylases; D006657:Histones / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010089:Oxidoreductases, N-Demethylating / Q000502:physiology*; D010950:Plasma Cells / Q000166:cytology* / Q000378:metabolism; D055232:Proline-Rich Protein Domains; D011485:Protein Binding; D012097:Repressor Proteins / Q000502:physiology*
D002843:Chromatin; D006657:Histones; D012097:Repressor Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human; D010089:Oxidoreductases, N-Demethylating