LSD1 is required for chromosome segregation during mitosis.
Dynamic methylation/demethylation of histones and non-histone proteins occurs during the cell cycle. Lysine-specific demethylase 1 (LSD1) exhibits diverse transcriptional activities through catalyzing demethylation of mono- and di-methylated histone H3 on lysine 4 (H3K4) and lysine 9 (H3K9). We show here that inhibition of LSD1 expression by siRNA leads to abnormal chromosomal segregation in unperturbed mitosis and abnormal centrosome duplication, and is associated with decreased protein levels of MAD2 and BUBR1. LSD1 positively regulates the BUBR1 and MAD2 promoter activity and maintains local monomethylation status of H3K9, which is a repressive histone mark for gene transcription. Expression of exogenous BUBR1 and MAD2 in LSD1-depleted cells partially rescues the defect of chromosome segregation. Our results suggest that LSD1 plays a role in chromosomal segregation during mitosis partially through transcriptional regulation of BUBR1 and MAD2.
Lv
Shuang
S
Laboratory of Cancer Biology, College of Life Sciences, Capital Normal University, 105 Xi San Huan Road (N), Beijing, China.
Bu
Wenjuan
W
Jiao
Hong
H
Liu
Bo
B
Zhu
Lin
L
Zhao
Hongchang
H
Liao
Ji
J
Li
Jing
J
Xu
Xingzhi
X
D002135:Calcium-Binding Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D018385:Centrosome / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D064246:Mad2 Proteins; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; D056466:Histone Demethylases; C495195:KDM1A protein, human; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases