CR Name:
Species:    Tissue or Cell: 

Chromatin Regulator

Alias

PHF8JHDM1F; MRXSSD; ZNF422; KIAA1111; DKFZp686E0868

External Links:

Wiki    GeneCards    NCBI    UniProt

Related histone modifications:

H3K9me2;H3K27me2;H4K20me1;H3K4me3;H3K4me2

Introduction

Full Name: PHD finger protein 8 . PHF8 is a demethylase that can remove Histone H3 lysine 9 dimethylation (H3K9me2), histone H3 lysine 9 monomethylation (H3K9me1), and histone H4 lysine 20 monomethylation (H4K20me1). It possesses a Jmjc domain and a PHD (plant homeodomain) domain and acts as a reader of histone H3 lysine 4 trimethylation (H3K4me3). It is involved in transcription activation, development, differentiation, cell growth and the cell cycle (1-9).

Function and Interaction

PHF8 participates in apoptosis in the brain and craniofacial development in zebrafish, which is partly dependent on its direct modulation of MSXB expression (1). PHF8 interacts directly with RNA polymerase II and H3K4 methyltransferase complex subunits WDR5 and Ash2L, and it is also known to activate Pol I transcription (2-3). The PHF8 demethylase localizes to the nucleolus, where it binds to the promoter region of rDNA genes, thus activating the transcription of rRNA genes by binding to H3K4me3 and demethylating H3K9me1 and H3K9me2 (3,5). PHF8 is associated with the retinoic acid receptor (RAR), and deletion of PHF8 could result in the disruption of RA-induced neuronal differentiation (4). PHF8 cooperates with E2F1, HCF-1, and in determining the G1-S transition of the cell cycle (6).

Disease Association

PHF8 mutations, on the X chromosome, are thought to be associated with Siderius-Hamel syndrome, which is a form of X-linked mental retardation (XLMR) that is often accompanied by cleft lip/cleft palate (10-11).

ChIP-Seq data


SpeciesCell lineCell typeTissueDataDownloadSend to CistromeAnalysis FiguresComparisonReference
Homo sapiensK562ErythroblastBone MarrowGSE32509 ,GSM831008
Click  DownloadClick22196736

ChIP-Seq data of related histone modifications


Products/SubstratesSpeciesCell lineCell typeTissueDataDownload Send to CistromeAnalysis FiguresReference
H3K4me3 Homo sapiens H1 Embryonic Stem Cell Embryo GSE41009 ,GSM1006722 Bed     Big wiggle
Click   Download23382218
H3K4me2 Homo sapiens HEK293T Epithelium Embryonic Kidney GSE50177 ,GSM1215134 Bed     Big wiggle
Click   Download24077223
H3K4me3 Homo sapiens HEK293T Epithelium Embryonic Kidney GSE51633 ,GSM1249885 Bed     Big wiggle
Click   Download24360279
H3K4me2 Homo sapiens HEK293T Epithelium Embryonic Kidney GSE51633 ,GSM1249886 Bed     Big wiggle
Click   Download24360279
H3K4me3 Homo sapiens HeLa Epithelium Cervix GSE61911 ,GSM1517092 Bed     Big wiggle
Click   Download26619937
H3K9me2 Homo sapiens SH-SY5Y Neuron Bone Marrow GSE58258 ,GSM1542253 Bed     Big wiggle
Click   Download25684206
H3K9me2 Homo sapiens SH-SY5Y Neuron Bone Marrow GSE58258 ,GSM1542255 Bed     Big wiggle
Click   Download25684206
H3K4me3 Homo sapiens HeLa Epithelium Cervix GSE71848 ,GSM1846800 Bed     Big wiggle
Click   Download26527278
H3K4me3 Homo sapiens HeLa Epithelium Cervix GSE71848 ,GSM1846804 Bed     Big wiggle
Click   Download26527278
H3K4me3 Homo sapiens HeLa Epithelium Cervix GSE20040 ,GSM501713 Bed     Big wiggle
Click   Download20418881
H3K4me3 Homo sapiens SH-SY5Y Neuron Bone Marrow GSE20673 ,GSM518558 Bed     Big wiggle
Click   Download20346720
H3K4me3 Homo sapiens Hs68 Fibroblast Foreskin GSE20753 ,GSM520385 Bed     Big wiggle
Click   Download20421419
H3K4me3 Homo sapiens Hs68 Fibroblast Foreskin GSE20753 ,GSM520386 Bed     Big wiggle
Click   Download20421419
H4K20me1 Homo sapiens HeLa Epithelium Cervix GSE22478 ,GSM558474 Bed     Big wiggle
Click   Download20622854
H3K4me3 Homo sapiens HeLa Epithelium Cervix GSE20303 ,GSM566169 Bed     Big wiggle
Click   Download20850016
H3K4me3 Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM605315 Bed     Big wiggle
Click   Download19829295
H4K20me1 Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM605329 Bed     Big wiggle
Click   Download19829295
H3K4me3 Homo sapiens K562 Erythroblast Bone Marrow GSE28162 ,GSM608165 Bed     Big wiggle
Click   Download21596310
H4K20me1 Homo sapiens K562 Erythroblast Bone Marrow GSE29611 ,GSM733675 Bed     Big wiggle
Click   Download22955616
H3K4me3 Homo sapiens HeLa Epithelium Cervix GSE31412 ,GSM779435 Bed     Big wiggle
Click   Download23539139
H3K4me3 Homo sapiens K562 Erythroblast Bone Marrow GSE35294 ,GSM865280 Bed     Big wiggle
Click   Download23754963
H3K4me3 Homo sapiens K562 Erythroblast Bone Marrow GSE35294 ,GSM865281 Bed     Big wiggle
Click   Download23754963
H3K4me3 Homo sapiens HEK293T Epithelium Embryonic Kidney GSE36620 ,GSM897574 Bed     Big wiggle
Click   Download23353889
H3K4me3 Homo sapiens HEK293T Epithelium Embryonic Kidney GSE36620 ,GSM897579 Bed     Big wiggle
Click   Download23353889
H3K4me3 Homo sapiens H1 Embryonic Stem Cell Embryo GSE16256 ,GSM906405 Bed     Big wiggle
Click   Download19829295

Notice: For bigwiggle or bed file download, if the browser cannot automatically download the file, users can right click the hyperlink and then click the "Save link as..." button, which will automatically redirect to download dialogue box, or click the "Copy link address" button and access the website in a new tab page. For data analysis in Cistrome, users should first login into the Cistrome website, then press the "Send Bed" or "Send Big wiggle" button. For data download by Cistrome, users can follow this tutorial.

References

1. Qi, H.H., Sarkissian, M., Hu, G.Q., Wang, Z.B., Bhattacharjee, A., Gordon, D.B., Gonzales, M., Lan, F., Ongusaha, P.P., Huarte, M. et al. (2010) Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature, 466, 503-U511.
2. Fortschegger, K., de Graaf, P., Outchkourov, N.S., van Schaik, F.M.A., Timmers, H.T.M. and Shiekhattar, R. (2010) PHF8 Targets Histone Methylation and RNA Polymerase II To Activate Transcription. Mol Cell Biol, 30, 3286-3298.
3. Feng, W.J., Yonezawa, M., Ye, J., Jenuwein, T. and Grummt, I. (2010) PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation. Nature Structural & Molecular Biology, 17, 445-U483.
4. Qiu, J.H., Shi, G.A., Jia, Y.H., Li, J., Wu, M., Li, J.W., Dong, S. and Wong, J.M. (2010) The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation. Cell Res, 20, 908-918.
5. Zhu, Z.Q., Wang, Y.R., Li, X., Wang, Y.Q., Xu, L.Y., Wang, X., Sun, T.L., Dong, X.B., Chen, L.L., Mao, H.L. et al. (2010) PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis (vol 20, pg 794, 2010). Cell Res, 20, 970-970.
6. Liu, W., Tanasa, B., Tyurina, O.V., Zhou, T.Y., Gassmann, R., Liu, W.T., Ohgi, K.A., Benner, C., Garcia-Bassets, I., Aggarwal, A.K. et al. (2010) PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression. Nature, 466, 508-U514.
7. Yu, L., Wang, Y., Huang, S., Wang, J.J., Deng, Z.Q., Zhang, Q., Wu, W., Zhang, X.L., Liu, Z., Gong, W.M. et al. (2010) Structural insights into a novel histone demethylase PHF8. Cell Res, 20, 166-173.
8. Loenarz, C., Ge, W., Coleman, M.L., Rose, N.R., Cooper, C.D.O., Klose, R.J., Ratcliffe, P.J. and Schofield, C.J. (2010) PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an N-epsilon-dimethyl lysine demethylase. Hum Mol Genet, 19, 217-222.
9. Kleine-Kohlbrecher, D., Christensen, J., Vandamme, J., Abarrategui, I., Bak, M., Tommerup, N., Shi, X.B., Gozani, O., Rappsilber, J., Salcini, A.E. et al. (2010) A Functional Link between the Histone Demethylase PHF8 and the Transcription Factor ZNF711 in X-Linked Mental Retardation. Mol Cell, 38, 165-178.
10. Siderius, L.E., Hamel, B.C.J., van Bokhoven, H., de Jager, F., van den Helm, B., Kremer, H., Heineman-de Boer, J.A., Ropers, H.H. and Mariman, E.C.M. (1999) X-linked mental retardation associated with cleft lip palate maps to Xp11.3-q21.3. Am J Med Genet, 85, 216-220.
11. Laumonnier, F., Holbert, S., Ronce, N., Faravelli, F., Lenzner, S., Schwartz, C.E., Lespinasse, J., Van Esch, H., Lacombe, D., Goizet, C. et al. (2005) Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate. J Med Genet, 42, 780-786.

Figure Gallery

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About Chromatin Regulator

Chromatin Regulator Cistrome
is a unique database integrating curated information of CRs, CR ChIP-seq datasets, CR related HM ChIP-seq datasets, and analysis of the relationship between CRs and HMs ChIP-seq pairs in human and mouse.

Contact

houshuang [at] tongji dot edu dot cn