UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development

@article{Agger2007UTXAJ,
  title={UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development},
  author={Karl Agger and Paul A. C. Cloos and Jesper Heile Christensen and Diego Pasini and Simon Rose and Juri Rappsilber and Irina Issaeva and Eli Canaani and Anna Elisabetta Salcini and Kristian Helin},
  journal={Nature},
  year={2007},
  volume={449},
  pages={731-734}
}
The trithorax and the polycomb group proteins are chromatin modifiers, which play a key role in the epigenetic regulation of development, differentiation and maintenance of cell fates. The polycomb repressive complex 2 (PRC2) mediates transcriptional repression by catalysing the di- and tri-methylation of Lys 27 on histone H3 (H3K27me2/me3). Owing to the essential role of the PRC2 complex in repressing a large number of genes involved in somatic processes, the H3K27me3 mark is associated with… 

The histone H3 Lys 27 demethylase JMJD3 regulates gene expression by impacting transcriptional elongation.

The model whereby JMJD3 activates bivalent gene transcription by demethylating H3K27me3 and promoting transcriptional elongation is supported, and new insight is provided into the mechanisms by whichJMJD3 regulates gene expression.

Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2.

It is shown that the PRC2 complex recruits Rbp2 to its target genes, and that this interaction is required forPRC2-mediated repressive activity during ES cell differentiation, an elegant mechanism for repression of developmental genes by the coordinated regulation of epigenetic marks involved in repression and activation of transcription.

KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation

It is shown that JMJD5 (now renamed KDM8), a JmjC family member, demethylates H3K36me2 and is required for cell cycle progression and is identified as an important cell cycle regulator.

The Histone H3 Lysine 27-Specific Demethylase Jmjd3 Is Required for Neural Commitment

Jmjd3, recently identified as a H3-K27me3 specific demethylase, controls the expression of key regulators and markers of neurogenesis and is required for commitment to the neural lineage, confirming the functional relevance of bivalent domain resolution.

Polycomb Repressive Complex 2 and H3K27me3 Cooperate with H3K9 Methylation To Maintain Heterochromatin Protein 1α at Chromatin

It is suggested that the existence of a cooperative mechanism of HP1α anchorage at chromatin involving H3 methylation on both K9 and K27 residues is possible and fit with recent proteomic studies identifying PRC2 as an indirect H3K9me3 binder in mouse tissues.

Transcriptomic Profiling and H3K27me3 Distribution Reveal Both Demethylase-Dependent and Independent Regulation of Developmental Gene Transcription in Cell Differentiation

It is suggested that both dem methylase-dependent and demethylase-independent transcriptional regulation play a role in early differentiation and developmental gene expression activated by H3K27me3 demethylation.

Histone Methylases and Demethylases Regulating Antagonistic Methyl Marks: Changes Occurring in Cancer

A picture is emerging which indicates that the changes which occur in cancer during methylation of histone lysines can lead to repression of genes, including tumour suppressor genes, or to the activation of oncogenes.

Histone Demethylase Activity of Utx Is Essential for Viability and Regulation of HOX Gene Expression in Drosophila

The earliest embryonic stages and the adult stage are identified as two phases during the Drosophila life cycle that critically require H3K27me3 demethylase activity.

Stage-Dependent and Locus-Specific Role of Histone Demethylase Jumonji D3 (JMJD3) in the Embryonic Stages of Lung Development

Findings demonstrate that Jmjd3 plays a stage-dependent and locus-specific role in the mouse lung development, and provides molecular insights into the mechanisms by which JmJd3 regulates target gene expression in the embryonic stages of lung development.
...

References

SHOWING 1-10 OF 21 REFERENCES

The putative oncogene GASC1 demethylates tri- and dimethylated lysine 9 on histone H3

In addition to identifying GASC1 as a histone trimethyl demethylase, this work suggests a model for how this enzyme might be involved in cancer development, and proposes it as a target for anti-cancer therapy.

Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions.

The Polycomb group (PcG) proteins form chromatin-modifying complexes that are essential for embryonic development and stem cell renewal and are commonly deregulated in cancer. Here, we identify their

Bypass of senescence by the polycomb group protein CBX8 through direct binding to the INK4A‐ARF locus

It is demonstrated that the chromodomain‐containing protein, CBX8, which is part of one of the PRC1 complexes, regulates proliferation of diploid human and mouse fibroblasts through direct binding to the INK4A‐ARF locus.

EZH2 is downstream of the pRB‐E2F pathway, essential for proliferation and amplified in cancer

It is demonstrated that both EZH2 and EED are essential for the proliferation of both transformed and non‐transformed human cells and, in addition, the pRB‐E2F pathway tightly regulates their expression and, consistent with this, it is found that EZh2 is highly expressed in a large set of human tumors.

Polycomb complexes repress developmental regulators in murine embryonic stem cells

It is shown that PcG proteins directly repress a large cohort of developmental regulators in murine ES cells, the expression of which would otherwise promote differentiation, and dynamic repression of developmental pathways by Polycomb complexes may be required for maintaining ES cell pluripotency and plasticity during embryonic development.

The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells.

The ability of the oncogene BMI1 to repress the INK4A-ARF locus requires its direct association and is dependent on the continued presence of the EZH2-containing Polycomb-Repressive Complex 2 (PRC2) complex.

Polycomb silencing mechanisms and the management of genomic programmes

Polycomb group complexes, which are known to regulate homeotic genes, have been found to control hundreds of other genes in mammals and insects, and function as global enforcers of epigenetically repressed states.

Knockdown of ALR (MLL2) Reveals ALR Target Genes and Leads to Alterations in Cell Adhesion and Growth

The results suggest that ALR is a transcriptional activator that induces the transcription of target genes by covalent histone modification, which appears to be involved in the regulation of adhesion-related cytoskeletal events, which might affect cell growth and survival.