Phosphorylation of LSD1 by PLK1 promotes its chromatin release during mitosis

Abstract

BackgroundLysine-specific histone demethylase 1 (LSD1) modulates chromatin status through demethylation of H3K4 and H3K9. It has been demonstrated that LSD1 is hyperphosphorylated and dissociates from chromatin during mitosis. However, the molecular mechanism of LSD1 detachment is unknown.ResultsIn this report, we found that polo-like kinase 1 (PLK1) directly interacted with LSD1 and phosphorylated LSD1 at Ser-126 . Nocodazole-induced metaphase arrest promoted release of LSD1 from chromatin, and the phosphorylation-defective mutant LSD1 (S126A) failed to dissociate from chromatin upon nocodazole treatment.ConclusionsTaken together, our findings demonstrate that phosphorylation of LSD1 at Ser-126 by PLK1 promotes its release from chromatin during mitosis.

Function and Regulation of Histone H3 Lysine-4 Methylation During Oocyte Meiosis and Maternal-to-Zygotic Transition

“…However, a serious concern is raised that no differences in the global levels of H3K4 methylation, including H3K4me1, H3K4me2 or H3K4me3, were observed between the control and Setd1b null oocytes and zygotes ( Brici et al, 2017 ). This is in sharp contrast to the Cxxc1 null oocytes, in which the H3K4me3 level decreases significantly ( Yu et al, 2017 ; Sha et al, 2018a ). Therefore, these results suggest two facts, i.e., ( Dai et al, 2018 ) SETD1A and SETD1B play overlapping roles in mediating H3K4 trimethylation during oogenesis, whereas CXXC1 is indispensable as a DNA-binding subunit of the SETD1/CAMPASS complex, and ( Sha et al, 2018b ) the absence of SETD1B may affect the distribution— instead of the global abundance—of H3K4m3 in the maternal genome and cause milder defects than the Cxxc1 knockout in oocytes.…”

“…In addition to MZT defects, meiotic resumption and spindle assembly are impaired in fully grown Cxxc1 -deleted oocytes ( Yu et al, 2017 ; Sha et al, 2018a ). The involvement of CXXC1 and H3K4me3 in the regulation of meiotic cell cycle progression is discussed in later sections.…”

“…In developing mouse oocytes, H3K4me3 levels on chromatin increase during the transition of chromatin configuration from the NSN to SN type ( Yu et al, 2017 ). Following meiosis resumption, H3K4me1 and H3K4me2 levels increase, but H3K4me3 levels decrease after GV breakdown (GVBD) and reach the lowest point in anaphase I ( Sha et al, 2018a ). The meiotic maturation-coupled fluctuation of H3K4 methylation levels suggested that these histone modifications perform previously unrecognized transcription-independent functions with respect to regulating the meiotic divisions of oocytes.…”

Targeting histone lysine-specific demethylase KDM1A/LSD1 to control epithelial-mesenchymal transition program in breast cancers

“…Several studies established that LSD1 activity and stability is altered by post-translational modifications [40,41] . LSD1 is acetylated in epithelial, but not in mesenchymal cells.…”

Histone methyl-transferases and demethylases in the autophagy regulatory network: the emerging role of KDM1A/LSD1 demethylase

“…Finally, several studies reported that KDM1A is subjected to different post-translational modifications, which may alter its activity or stability [86,87]. It has been shown that acetylation of KDM1A by KAT8/MOF impairs KDM1A ability to associate with nucleosomes, resulting in enhanced expression of epithelial genes and suppressing epithelial-to-mesenchymal transition [88].…”