Abstract
Pre-B-cell leukemia homeobox (PBX) and myeloid ecotropic viral integration site (MEIS) proteins control cell fate decisions in many physiological and pathophysiological contexts, but how these proteins function mechanistically remains poorly defined. Focusing on the first hours of neuronal differentiation of adult subventricular zone-derived stem/progenitor cells, we describe a sequence of events by which PBX-MEIS facilitates chromatin accessibility of transcriptionally inactive genes: In undifferentiated cells, PBX1 is bound to the H1-compacted promoter/proximal enhancer of the neuron-specific gene doublecortin (Dcx) Once differentiation is induced, MEIS associates with chromatin-bound PBX1, recruits PARP1/ARTD1, and initiates PARP1-mediated eviction of H1 from the chromatin fiber. These results for the first time link MEIS proteins to PARP-regulated chromatin dynamics and provide a mechanistic basis to explain the profound cellular changes elicited by these proteins.
© 2017 Hau et al.
MeSH terms
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Adult Stem Cells / enzymology*
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Animals
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Binding Sites
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Cell Line, Tumor
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Cell Lineage*
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Chromatin / enzymology*
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Chromatin / genetics
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Chromatin Assembly and Disassembly
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Doublecortin Domain Proteins
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Doublecortin Protein
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Female
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Gene Expression Regulation, Developmental
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HEK293 Cells
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Histones / metabolism*
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism*
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / metabolism*
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Neural Stem Cells / enzymology*
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Neurogenesis*
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Neuropeptides / genetics
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Neuropeptides / metabolism*
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Phenotype
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Poly (ADP-Ribose) Polymerase-1 / genetics
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Poly (ADP-Ribose) Polymerase-1 / metabolism*
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Pre-B-Cell Leukemia Transcription Factor 1
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Promoter Regions, Genetic
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Protein Binding
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RNA Interference
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Spheroids, Cellular
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Stem Cell Niche
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Time Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic
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Transfection
Substances
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Chromatin
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DCX protein, human
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Dcx protein, mouse
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Doublecortin Domain Proteins
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Doublecortin Protein
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Histones
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Homeodomain Proteins
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Microtubule-Associated Proteins
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Mrg1 protein, mouse
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Neuropeptides
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Pbx1 protein, mouse
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Pre-B-Cell Leukemia Transcription Factor 1
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Transcription Factors
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Parp1 protein, mouse
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Poly (ADP-Ribose) Polymerase-1
Associated data
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RefSeq/NM_027426
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RefSeq/NM_001109988