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*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2715-2729
Number of pages15
JournalJournal of Cell Biology
Volume216
Issue number9
DOIs
Publication statusPublished - 1 Sep 2017
Externally publishedYes

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