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

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

iDHS-DASTS: identifying DNase I hypersensitive sites based on LASSO and stacking learning

The general framework of our work on iDHS-DASTS.

Atlas and developmental dynamics of mouse DNase I hypersensitive sites

Early mammalian development is orchestrated by genome-encoded regulatory elements populated by a changing complement of regulatory factors, creating a dynamic chromatin landscape. To define the spatiotemporal organization of regulatory DNA landscapes during mouse development and maturation, we generated nucleotide-resolution DNA accessibility maps from 15 tissues sampled at 9 intervals spanning post-conception day 9.5 through early adult, and integrated these with 41 adult-stage DNase-seq profiles to create a global atlas of mouse regulatory DNA. Collectively, we delineated >1.8 million DNase I hypersensitive sites (DHSs), with the vast majority displaying temporal and tissue-selective patterning. Here we show that tissue regulatory DNA compartments show sharp embryonic-to-fetal transitions characterized by wholesale turnover of DHSs and progressive domination by a diminishing number of transcription factors. We show further that aligning mouse and human fetal development on a regulatory axis exposes disease-associated variation enriched in early intervals lacking human samples. Our results provide an expansive new resource for decoding mammalian developmental regulatory programs.