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Cited by 46Genetics and Neurodevelopmental DisordersEpigenetics and DNA MethylationGenomics and Chromatin Dynamics

The histone demethylase PHF8 is essential for cytoskeleton dynamics

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Asensio-Juan, Elena, Gallego, Carme, Martínez-Balbás, Marian A.·2012·Nucleic Acids Research
DOI 10.1093/nar/gks716PMC PMC3479184
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Abstract

PHF8 is a histone demethylase associated with X-linked mental retardation. It has been described as a transcriptional co-activator involved in cell cycle progression, but its physiological role is still poorly understood. Here we show that PHF8 controls the expression of genes involved in cell adhesion and cytoskeleton organization such as RhoA, Rac1 and GSK3β. A lack of PHF8 not only results in a cell cycle delay but also in a disorganized actin cytoskeleton and impaired cell adhesion. Our data demonstrate that PHF8 directly regulates the expression of these genes by demethylating H4K20me1 at promoters. Moreover, c-Myc transcription factor cooperates with PHF8 to regulate the analysed promoters. Further analysis in neurons shows that depletion of PHF8 results in down-regulation of cytoskeleton genes and leads to a deficient neurite outgrowth. Overall, our results suggest that the mental retardation phenotype associated with loss of function of PHF8 could be due to abnormal neuronal connections as a result of alterations in cytoskeleton function.

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  • In neuronal cells, c-Myc cooperated with the co-activator PHF8 for RHOA expression.

    “In neuronal cells, c-Myc cooperated with the co-activator PHD finger protein 8 (PHF8) for RHOA expression [86].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [86]

    In Results (‘PHF8 cooperates with Myc transcription factor to regulate transcription’), the paper links c-Myc and PHF8 to RhoA expression and promoter binding, but those cooperation experiments used HeLa cells. In Results (‘Down-regulation of PHF8 leads to alterations in neurite outgrowth’), RhoA expression is PHF8-dependent in neuronal SH-SY5Y cells; the paper does not show c-Myc cooperating with PHF8 for RhoA expression in those cells. (LLM, conf=0.88)

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Research works printed but not linked: 36

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Cited by

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Authors
Asensio-Juan, E., Gallego, C., & Martínez-Balbás, M. A.
Affiliations
Consejo Superior de Investigaciones Científicas (ES)
ORCID
Gallego, Carme
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2012-07-31
Volume
40
Issue
19
Pages
9429-9440
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gks716
PMC
PMC3479184
OpenAlex
W1974850149
Cited by
46
References
3
Citations by year
2026: 1 · 2024: 1 · 2023: 6 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 7 · 2014: 8 · 2013: 1 · 2012: 2
FWCI
3.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
PHF8, histone demethylase, H4K20me1, cytoskeletal dynamics, actin cytoskeleton, cell adhesion, RhoA, Rac1, GSK3β, c-Myc, transcriptional regulation, X-linked intellectual disability, neurite outgrowth, neurons, cell cycle
MeSH terms
Glycogen Synthase Kinase 3 beta, Animals, Cell Adhesion, Cell Line, Cells, Cultured, Gene Expression Regulation, HeLa Cells, Humans, Actin Cytoskeleton, Transcription Factors, Transcription, Genetic, Down-Regulation, Proto-Oncogene Proteins c-myc, Neurites, rho GTP-Binding Proteins, Glycogen Synthase Kinase 3, alpha Catenin, Mice, Histone Demethylases

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