Abstract
Mutations in the XNP/ATR-X gene cause several X-linked mental retardation syndromes in humans. The XNP/ATR-X gene encodes a DNA-helicase belonging to the SNF2 family. It has been proposed that XNP/ATR-X might be involved in chromatin remodelling. The lack of a mouse model for the ATR-X syndrome has, however, hampered functional studies of XNP/ATR-X. C. elegans possesses one homolog of the XNP/ATR-X gene, named xnp-1. By analysing a deletion mutant, we show that xnp-1 is required for the development of the embryo and the somatic gonad. Moreover, we show that abrogation of xnp-1 function in combination with inactivation of genes of the NuRD complex, as well as lin-35/Rb and hpl-2/HP1 leads to a stereotyped block of larval development with a cessation of growth but not of cell division. We also demonstrate a specific function for xnp-1 together with lin-35 or hpl-2 in the control of transgene expression, a process known to be dependent on chromatin remodelling. This study thus demonstrates that in vivo XNP-1 acts in association with RB, HP1 and the NuRD complex during development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Animals, Genetically Modified
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / growth & development*
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / physiology
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DNA Helicases / genetics
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DNA Helicases / physiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology
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Genes, Helminth
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Gonads / growth & development
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Helminth Proteins / genetics
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Helminth Proteins / physiology*
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Hepatocyte Nuclear Factor 1
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Hepatocyte Nuclear Factor 1-alpha
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Histone Deacetylases / genetics
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Histone Deacetylases / physiology
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Humans
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Larva / growth & development
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Mi-2 Nucleosome Remodeling and Deacetylase Complex
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Mutation
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology
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RNA Interference
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / physiology
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Transcription Factors / genetics
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Transcription Factors / physiology
Substances
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Caenorhabditis elegans Proteins
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DNA-Binding Proteins
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HNF1A protein, human
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Helminth Proteins
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Hepatocyte Nuclear Factor 1-alpha
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Nuclear Proteins
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Retinoblastoma Protein
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Transcription Factors
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Hepatocyte Nuclear Factor 1
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Histone Deacetylases
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Mi-2 Nucleosome Remodeling and Deacetylase Complex
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DNA Helicases
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XNP-1 protein, C elegans