MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1.
Ann-Christin HauBritta Moyo GrebbinZsuzsa AgostonMarie Anders-MaurerTamara MüllerAnja GroßJasmine KolbJulian D LangerClaudia DöringDorothea SchultePublished in: The Journal of cell biology (2017)
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.
Keyphrases
- dna damage
- transcription factor
- genome wide
- gene expression
- dna repair
- dna methylation
- genome wide identification
- acute myeloid leukemia
- bone marrow
- cell fate
- sars cov
- high glucose
- young adults
- cell cycle arrest
- cell death
- signaling pathway
- copy number
- diabetic rats
- endoplasmic reticulum stress
- intellectual disability