A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation

By D. Kleine-Kohlbrecher, J. Christensen, J. Vandamme, Iratxe Abarrategui, M. Bak, Niels Tommerup, Xiaobing Shi, O. Gozani, Juri Rappsilber, A. Salcini and 1 more. Molecules and Cells, 2010

765 citations recorded by the source corpus.

Summary X-linked mental retardation (XLMR) is an inherited disorder that mostly affects males and is caused by mutations in genes located on the X chromosome. Here, we show that the XLMR protein PHF8 and a C. elegans homolog F29B9.2 catalyze demethylation of di- and monomethylated lysine 9 of histone H3 (H3K9me2/me1). The PHD domain of PHF8 binds to H3K4me3 and colocalizes with H3K4me3 at transcription initiation sites. Furthermore, PHF8 interacts with another XMLR protein, ZNF711, which binds to a subset of PHF8 target genes, including the XLMR gene JARID1C. Of interest, the C. elegans PHF8 homolog is highly expressed in neurons, and mutant animals show impaired locomotion. Taken together, our results functionally link the XLMR gene PHF8 to two other XLMR genes, ZNF711 and JARID1C, indicating that MR genes may be functionally linked in pathways, causing the complex phenotypes observed in patients developing MR.

Subfields: Cognitive Neuroscience, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2f55169e422b4658453238130034ef02a4b607dd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cognitive Neuroscience

Richard A. Young

In Genetics

In Molecular Biology

Citations in the corpus

A double take on bivalent promoters. (2013, background): “In addition to interacting with the MLL complexes, OCT4 has also been shown to interact with PRC1 subcomplexes as well as with the histone deacetylase-containing NuRD complex (Pardo et al. 2010; van den Berg et al. 2010).”
Control of Embryonic Stem Cell State (2011, background): “…of ES cell state (Table 1) are shown. genetic and proteomic screens (Bilodeau et al., 2009; Chia et al., 2010; Fazzio et al., 2008; Hu et al., 2009; Ivanova et al., 2006; Kagey et al., 2010; Liang et al., 2008; Pardo et al., 2010; van den Berg et al., 2010; Wang et al., 2006; Zhao et al., 2010).”
Dedifferentiation, transdifferentiation and reprogramming: three routes to regeneration (2011, background): “OCT4 has an essential role in the development and maintenance of pluripotency by activating or repressing numerous gene”
ChIPBase: a database for decoding the transcriptional regulation of long non-coding RNA and microRNA genes from ChIP-Seq data (2012, neutral): “GSE20673 GSM518560 neuroblastoma cell line SH-SY5Y ZNF711 (1) GSE14283 GSM357351 HeLa cells OCT1 (2)”
Epigenetic modifications and human disease (2010, neutral): “and the histone demethylase PHF8 has been involved in X-linked mental retardatio”
Nucleosome-Interacting Proteins Regulated by DNA and Histone Methylation (2010, neutral): “Finally, the PRC2 complex is enriched on H3K27me3 nucleosomes (and to a lesser extent on H3K9me3 nucleosomes), but incorporation of methyl-CpG DNA counteracts this recruitment, as shown for the EED (Figure 2E) and the SUZ12 (Figure 2F) subunits.”
Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC (2013, neutral): “Alternatively, affinity-isolated proteins were reduced and alkylated on beads similarly as described above.”