Abstract
We have analyzed the role of actin polymerization in retinoic acid (RA)-induced HoxB transcription, which is mediated by the HoxB regulator Prep1. RA induction of the HoxB genes can be prevented by the inhibition of actin polymerization. Importantly, inhibition of actin polymerization specifically affects the transcription of inducible Hox genes, but not that of their transcriptional regulators, the RARs, nor of constitutively expressed, nor of actively transcribed Hox genes. RA treatment induces the recruitment to the HoxB2 gene enhancer of a complex composed of "elongating" RNAPII, Prep1, beta-actin, and N-WASP as well as the accessory splicing components p54Nrb and PSF. We show that inhibition of actin polymerization prevents such recruitment. We conclude that inducible Hox genes are selectively sensitive to the inhibition of actin polymerization and that actin polymerization is required for the assembly of a transcription complex on the regulatory region of the Hox genes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism*
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Cytochalasin D / pharmacology
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DNA-Binding Proteins
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Down-Regulation
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / metabolism
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Humans
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Immunoblotting
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Mutation
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Nuclear Matrix-Associated Proteins / genetics
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Nuclear Matrix-Associated Proteins / metabolism
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Nucleic Acid Synthesis Inhibitors / pharmacology
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Octamer Transcription Factors / genetics
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Octamer Transcription Factors / metabolism
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PTB-Associated Splicing Factor
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Polymers / metabolism
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RNA Interference
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RNA Polymerase II / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Receptors, Retinoic Acid / genetics
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Receptors, Retinoic Acid / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / genetics*
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Transcription, Genetic / drug effects*
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Tretinoin / pharmacology*
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Wiskott-Aldrich Syndrome Protein, Neuronal / genetics
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Wiskott-Aldrich Syndrome Protein, Neuronal / metabolism
Substances
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Actins
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Antineoplastic Agents
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DNA-Binding Proteins
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HOXB1 homeodomain protein
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HOXB2 protein, human
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HOXB6 protein, human
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Homeodomain Proteins
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HoxB3 protein, human
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NONO protein, human
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Nuclear Matrix-Associated Proteins
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Nucleic Acid Synthesis Inhibitors
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Octamer Transcription Factors
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PKNOX1 protein, human
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PTB-Associated Splicing Factor
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Polymers
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RNA, Messenger
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RNA-Binding Proteins
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Receptors, Retinoic Acid
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Transcription Factors
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Wiskott-Aldrich Syndrome Protein, Neuronal
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Cytochalasin D
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Tretinoin
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RNA Polymerase II