Abstract
Trimethylation of histone H3 lysine 4 (H3K4me3) correlates strongly with gene expression in many different organisms, yet the question of whether it plays a causal role in transcriptional activity remains unresolved. Although H3K4me3 does not directly affect chromatin accessibility, it can indirectly affect genome accessibility by recruiting the ATP-dependent chromatin remodeling complex NuRF (Nucleosome Remodeling Factor). The largest subunit of NuRF, BPTF/NURF301, binds H3K4me3 specifically and recruits the NuRF complex to loci marked by this modification. Studies have shown that the strength and duration of BPTF binding likely also depends on additional chromatin features at these loci, such as lysine acetylation and variant histone proteins. However, the exact details of this recruitment mechanism vary between studies and have largely been tested in vitro. Here, we use stem cells isolated directly from live planarian animals to investigate the role of BPTF in regulating chromatin accessibility in vivo. We find that BPTF operates at gene promoters and is most effective at facilitating transcription at genes marked by Set1-dependent H3K4me3 peaks, which are significantly broader than those added by the lysine methyltransferase MLL1/2. Moreover, BPTF is essential for planarian stem cell biology and its loss of function phenotype mimics that of Set1 knockdown. Together, these data suggest that BPTF and H3K4me3 are important mediators of both transcription and in vivo stem cell function.