Dual-specificity histone demethylase KIAA1718 (KDM7A) regulates neural differentiation through FGF4

Huang, Chi‐Chun; Xiang, Yang; Wang, Yanru; Li, Xia; Xu, Longyong; Zhu, Ziqi; Zhang, Ting; Zhu, Qingqing; Zhang, Kejing; Jing, Naihe; Chen, Charlie Degui

doi:10.1038/cr.2010.5

Cited by 110 publications

(113 citation statements)

References 60 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…In agreement with the latter studies, we showed that in all assays PHF8 exhibited histone demethylase activity with H3K9me2/1 specificity. In this regard, PHF2 was reported to be an H3K9me1 demethylase [34], whereas KIAA1718/KDM7A exhibits a dual H3K9 and H3K27 demethylase activity [35].…”

Section: Discussionmentioning

confidence: 99%

The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation

et al. 2010

View full text Add to dashboard Cite

Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation (XLMR) and cleft lip/cleft palate. However, the underlying mechanism is unknown. Here we show that PHF8 is a histone demethylase and coactivator for retinoic acid receptor (RAR). Although activities for both H3K4me3/2/1 and H3K9me2/1 demethylation were detected in cellularbased assays, recombinant PHF8 exhibited only H3K9me2/1 demethylase activity in vitro, suggesting that PHF8 is an H3K9me2/1 demethylase whose specificity may be modulated in vivo. Importantly, a mutant PHF8 (phenylalanine at position 279 to serine) identified in the XLMR patients is defective in enzymatic activity, indicating that the loss of histone demethylase activity is causally linked with the onset of disease. In addition, we show that PHF8 binds specifically to H3K4me3/2 peptides via an N-terminal PHD finger domain. Consistent with a role for PHF8 in neuronal differentiation, knockdown of PHF8 in mouse embryonic carcinoma P19 cells impairs RA-induced neuronal differentiation, whereas overexpression of the wild-type but not the F279S mutant PHF8 drives P19 cells toward neuronal differentiation. Furthermore, we show that PHF8 interacts with RARα and functions as a coactivator for RARα. Taken together, our results suggest that histone methylation modulated by PHF8 plays a critical role in neuronal differentiation.

show abstract

Section: Discussionmentioning

confidence: 99%

The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Previously we identified KIAA1718 (KDM7A) as a dual-specificity histone demethylase for H3K9me2 and H3K27me2 that regulates neural differentiation by controlling the expression of FGF4 [28]. To further understand how KDM7A binds chromatin and regulates transcription, we studied its Caenorhabditis elegans ortholog.…”

Section: Introductionmentioning

confidence: 99%

Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans

Lin

Wang

et al. 2010

Cell Res

Self Cite

View full text Add to dashboard Cite

H3K9me2 and H3K27me2 are important epigenetic marks associated with transcription repression, whileH3K4me3 is associated with transcription activation. It has been shown that active and repressive histone methylations distribute in a mutually exclusive manner, but the underlying mechanism was poorly understood. Here we identified ceKDM7A, a PHD (plant homeodomain)-and JmjC domain-containing protein, as a histone demethylase specific for H3K9me2 and H3K27me2. We further demonstrated that the PHD domain of ceKDM7A bound H3K4me3 and H3K4me3 co-localized with ceKDM7A at the genome-wide level. Disruption of the PHD domain binding to H3K4me3 reduced the demethylase activity in vivo, and loss of ceKDM7A reduced the expression of its associated target genes. These results indicate that ceKDM7A is recruited to the promoter to demethylate H3K9me2 and H3K27me2 and activate gene expression through the binding of the PHD domain to H3K4me3. Thus, our study identifies a dual-specificity histone demethylase and provides novel insights into the regulation of histone methylation.

show abstract

“…Huang et al showed that KIAA1718 (KDM7A) is required for the demethylation of H3K9me2 and H3K27me2 at the promoter region of the FGF4 gene by ChIP assay, and KIAA1718 is required for FGF4 transcription in mouse embryonic stem cells [12]. Since the expression levels of KIAA1718 are significantly higher than those of PHF8 in neuronal precursor cells [12], KIAA1718 might be responsible for the specific regulation of these H3 epigenetic markers at the FGF4 gene at this stage. Tissue or stage specific functions may be a reason for the large number of different JmjCdomain-containing demethylases.…”

mentioning

confidence: 99%

Features of the PHF8/KIAA1718 histone demethylase

Suganuma

Workman

2010

Cell Res

View full text Add to dashboard Cite

Dual-specificity histone demethylase KIAA1718 (KDM7A) regulates neural differentiation through FGF4

Cited by 110 publications

References 60 publications

The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation

The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation

Coordinated regulation of active and repressive histone methylations by a dual-specificity histone demethylase ceKDM7A from Caenorhabditis elegans

Features of the PHF8/KIAA1718 histone demethylase

Contact Info

Product

Resources

About