We then used the same files in the CUT&RUN pipeline, here are the relevant commands:

bamCoverage     --bam H3K27me3_R1.target.markdup.sorted.bam     --outFileFormat bedgraph 
--skipNAs
--binSize 50 --normalizeUsing CPM --extendReads     --scaleFactor 1     --numberOfProcessors 2     --outFileName H3K27me3_R1.bedgraph

...

bedGraphToBigWig \
    H3K27me3_R1.clipped.bedGraph \
    Homo_sapiens.GRCh38.dna.primary_assembly.fa.sizes \
    H3K27me3_R1.bigWig

The equivalent command to drop Zero-covered bins within Deeptools is the option

--skipNAs

, and this seems to be the default in CUT&RUN. When we lose this option, the background looks again much lower (which for the experimentalists means ‘much nicer’):