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Super-enhancers (SEs), which consist of multiple enhancer elements, are occupied by master transcription factors and co-activators, such as Mediator, and are highly acetylated at histone H3K27. Here, we have characterized the SEs in terms of DNase I hypersensitive sites (DHSs) by analyzing publicly available chromatin immunoprecipitation (ChIP)-seq and DNase-seq data of K562 cells and compared with the DHSs in typical enhancers (TEs). DHSs in the SEs were highly marked by histone H3K4me1 than DHSs in TEs. Loss of H3K4me1 by the deletion of catalytic domains in histone methyltransferases MLL3 and MLL4 remarkably decreased histone H3K27ac and histone H3 depletion at SE DHSs than at TE DHSs. The levels of enhancer RNA (eRNA) transcripts and mRNA transcripts from the putative target genes were notably reduced at and near SE DHSs than TE DHSs following H3K4me1 loss. These results indicate that histone H3K4me1 is a marker for DHSs in SEs and that this modification has a more significant impact on the activation of SE DHSs than TE DHSs.

Histone H3K4me1 strongly activates the DNase I hypersensitive sites in super-enhancers than those in typical enhancers