Dataset Information


Illumina microarray experiment on LSD1 deletion ES cell with Lsd1Lox/Δ3 and Lsd1Δ3/Δ3

ABSTRACT: Lysine specific demethylase 1 (LSD1), which demethylates mono- and di- methylated histone H3-Lys4 as part of a complex including CoREST and histone deacetylases (HDAC), is essential for embryonic development in the mouse beyond e6.5 days. Here, we demonstrate that LSD1 expression and therefore function, is restricted to the epiblast of the post- implantation embryo. Conditional deletion of LSD1 in mouse embryonic stem (ES) cells, in vitro counterpart of the epiblast, revealed a reduction in CoREST protein, a subsequent decrease in associated HDAC activity and a global increase in Histone H3 Lys56 acetylation. Despite this biochemical perturbation, LSD1 deleted ES cells proliferate normally and retain stem cell characteristics. Loss of LSD1 causes the aberrant expression of 588 genes, including a number of transcription factors with roles in tissue development such as brachyury, Hoxb7, Hoxd8 and RARγ. Brachyury, a key-regulator of mesodermal differentiation, is a direct target gene of LSD1 and is over-expressed in e6.5 day Lsd1 genetrap embryos. Thus, LSD1 is required for the appropriate expression of key developmental regulators, via the stabilization of the LSD1/CoREST/HDAC complex, during early embryonic development. RNA samples from Lsd1Lox/Δ3 and Lsd1Δ3/Δ3 cells were compared, three biological replicates were performed.

ORGANISM(S): Mus musculus  

SUBMITTER: Jinli Luo  

PROVIDER: E-GEOD-21131 | ArrayExpress | 2010-12-06



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Lysine-specific demethylase 1 regulates the embryonic transcriptome and CoREST stability.

Foster Charles T CT   Dovey Oliver M OM   Lezina Larissa L   Luo Jin Li JL   Gant Timothy W TW   Barlev Nick N   Bradley Allan A   Cowley Shaun M SM  

Molecular and cellular biology 20100816 20

Lysine-specific demethylase 1 (LSD1), which demethylates mono- and dimethylated histone H3-Lys4 as part of a complex including CoREST and histone deacetylases (HDACs), is essential for embryonic development in the mouse beyond embryonic day 6.5 (e6.5). To determine the role of LSD1 during this early period of embryogenesis, we have generated loss-of-function gene trap mice and conditional knockout embryonic stem (ES) cells. Analysis of postimplantation gene trap embryos revealed that LSD1 expres  ...[more]

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