Article

Jarid1b targets genes regulating development and is involved in neural differentiation

Biotech Research and Innovation Centre, University of Copenhagen, Denmark.
The EMBO Journal (Impact Factor: 10.75). 11/2011; 30(22):4586-600. DOI: 10.1038/emboj.2011.383
Source: PubMed

ABSTRACT H3K4 methylation is associated with active transcription and in combination with H3K27me3 thought to keep genes regulating development in a poised state. The contribution of enzymes regulating trimethylation of lysine 4 at histone 3 (H3K4me3) levels to embryonic stem cell (ESC) self-renewal and differentiation is just starting to emerge. Here, we show that the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) is dispensable for ESC self-renewal, but essential for ESC differentiation along the neural lineage. By genome-wide location analysis, we demonstrate that Jarid1b localizes predominantly to transcription start sites of genes encoding developmental regulators, of which more than half are also bound by Polycomb group proteins. Virtually all Jarid1b target genes are associated with H3K4me3 and depletion of Jarid1b in ESCs leads to a global increase of H3K4me3 levels. During neural differentiation, Jarid1b-depleted ESCs fail to efficiently silence lineage-inappropriate genes, specifically stem and germ cell genes. Our results delineate an essential role for Jarid1b-mediated transcriptional control during ESC differentiation.

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    • "Additionally, the impact of arsenic on MLL expression has not been measured to date. Similarly, histone demethylase enzymes (HDM), including Jumonji-containing proteins, have been shown to be altered by toxin exposure (Chen et al., 2010); KDM5B (JARID1B), one of several histone demethylase enzymes responsible for removing methyl groups from H3K4, protects against aberrant H3K4me3 during development (Albert et al., 2013) and is involved in neuronal differentiation (Schmitz et al., 2011). Thus, we chose to assess both MLL and KDM5B expression in accordance with H3K4me3. "
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    • "ylation after inhibition of Acti - vin / Nodal signaling is consistent with the sequential H3K4me3 and H3K4me2 demethylation that is known to be mediated by this class of demethylases ( Cloos et al . 2008 ) . Interestingly , knockdown in Jarid1B expres - sion in mESCs impairs silencing of pluripotency genes and differentiation into neuroectoderm ( Schmitz et al . 2011 ) . Therefore , the epigenetic status of a core pluripo - tency network could be tightly controlled by extracellular signals through the dynamic competition of histone methylation writers and erasers ."
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    • "JARID1B, the H3K4me2 demethylase, has been shown to affect the expression of Oct4 and Nanog. Specifically, JARID1B plays a hand in suppressing the expression of these transcription factors as deletion allows Oct4 and Nanog expression to continue past their normal time course in an in vivo developmental model (Schmitz et al., 2011). The H3K9 demethylase JMJD1C has also shown a direct binding capacity to Oct4 (Wang et al., 2014a). "
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