MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1

Ann-Christin Hau; Britta Moyo Grebbin; Zsuzsa Agoston; Marie Anders-Maurer; Tamara Müller; Anja Groß; Jasmine Kolb; Julian D Langer; Claudia Döring; Dorothea Schulte

doi:10.1083/jcb.201701154

MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1

J Cell Biol. 2017 Sep 4;216(9):2715-2729. doi: 10.1083/jcb.201701154. Epub 2017 Jul 24.

Affiliations

¹ Institute of Neurology, Edinger Institute, University Hospital Frankfurt, J.W. Goethe University, Frankfurt, Germany.
² Department of Molecular Membrane Biology, Max Planck Institute for Biophysics, Frankfurt, Germany.
³ Senckenberg Institute of Pathology, University Hospital Frankfurt, J.W. Goethe University, Frankfurt, Germany.
⁴ Institute of Neurology, Edinger Institute, University Hospital Frankfurt, J.W. Goethe University, Frankfurt, Germany dorothea.schulte@kgu.de.

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.

MeSH terms

Adult Stem Cells / enzymology*
Animals
Binding Sites
Cell Line, Tumor
Cell Lineage*
Chromatin / enzymology*
Chromatin / genetics
Chromatin Assembly and Disassembly
Doublecortin Domain Proteins
Doublecortin Protein
Female
Gene Expression Regulation, Developmental
HEK293 Cells
Histones / metabolism*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism*
Humans
Male
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism*
Neural Stem Cells / enzymology*
Neurogenesis*
Neuropeptides / genetics
Neuropeptides / metabolism*
Phenotype
Poly (ADP-Ribose) Polymerase-1 / genetics
Poly (ADP-Ribose) Polymerase-1 / metabolism*
Pre-B-Cell Leukemia Transcription Factor 1
Promoter Regions, Genetic
Protein Binding
RNA Interference
Spheroids, Cellular
Stem Cell Niche
Time Factors
Transcription Factors / genetics
Transcription Factors / metabolism*
Transcription, Genetic
Transfection

Substances

Chromatin
DCX protein, human
Dcx protein, mouse
Doublecortin Domain Proteins
Doublecortin Protein
Histones
Homeodomain Proteins
Microtubule-Associated Proteins
Mrg1 protein, mouse
Neuropeptides
Pbx1 protein, mouse
Pre-B-Cell Leukemia Transcription Factor 1
Transcription Factors
Parp1 protein, mouse
Poly (ADP-Ribose) Polymerase-1

Associated data

RefSeq/NM_027426
RefSeq/NM_001109988