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10:48
Differentiation of a Human Neural Stem Cell Line on Three Dimensional Cultures, Analysis of MicroRNA and Putative Target Genes
Published on: April 12, 2015
Jarid1b targets genes regulating development and is involved in neural differentiation
Sandra U Schmitz1, Mareike Albert, Martina Malatesta
1Biotech Research and Innovation Centre, University of Copenhagen, Denmark.
The EMBO Journal
|October 25, 2011
Summary
Histone demethylase Jarid1b is not essential for embryonic stem cell self-renewal but crucial for neural differentiation. Depletion of Jarid1b increases H3K4me3 levels and impairs silencing of developmental genes.
Area of Science:
- Epigenetics
- Stem Cell Biology
- Developmental Biology
Background:
- Histone H3 lysine 4 trimethylation (H3K4me3) is linked to active gene transcription.
- H3K4me3 and H3K27me3 together maintain developmental genes in a poised state.
- The role of H3K4me3-regulating enzymes in embryonic stem cell (ESC) function is under investigation.
Purpose of the Study:
- To investigate the role of the H3K4me2/3 histone demethylase Jarid1b in ESC self-renewal and differentiation.
- To identify the genomic targets of Jarid1b and its association with H3K4me3.
- To understand Jarid1b's function in regulating gene expression during neural differentiation.
Main Methods:
- Genome-wide location analysis (ChIP-seq) to map Jarid1b binding sites.
- Analysis of H3K4me3 levels in ESCs with and without Jarid1b.
- Assessment of gene silencing during neural differentiation in Jarid1b-depleted ESCs.
Main Results:
- Jarid1b is dispensable for ESC self-renewal but essential for neural lineage differentiation.
- Jarid1b predominantly binds transcription start sites of developmental regulator genes, often co-occupied by Polycomb group proteins.
- Jarid1b depletion globally increases H3K4me3 levels and leads to failure in silencing stem and germ cell genes during neural differentiation.
Conclusions:
- Jarid1b plays a critical role in regulating H3K4me3 levels.
- Jarid1b is essential for the proper silencing of lineage-inappropriate genes during ESC differentiation.
- Jarid1b-mediated transcriptional control is vital for successful ESC differentiation, particularly along the neural lineage.
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