Atlas and developmental dynamics of mouse DNase I hypersensitive sites

Breeze, C. E.; Lazar, J.; Mercer, T.; Halow, J.; Washington, I.; Lee, K.; Ibarrientos, S.; Castillo, A.; Neri, F.; Haugen, E.; Rynes, E.; Reynolds, A.; Bates, D.; Diegel, M.; Dunn, D.; Kaul, R.; Sandstrom, R.; Meuleman, W.; Bender, M. A.; Groudine, M.; Stamatoyannopoulos, J. A.

doi:10.1101/2020.06.26.172718

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bioRxiv · 10.1101/2020.06.26.172718

Atlas and developmental dynamics of mouse DNase I hypersensitive sites

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Abstract

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.

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Breeze, C. E., Lazar, J., Mercer, T., Halow, J., Washington, I., Lee, K., Ibarrientos, S., Castillo, A., Neri, F., Haugen, E., Rynes, E., Reynolds, A., Bates, D., Diegel, M., Dunn, D., Kaul, R., Sandstrom, R., Meuleman, W., Bender, M. A., Groudine, M., Stamatoyannopoulos, J. A.. 2020-06-27. Atlas and developmental dynamics of mouse DNase I hypersensitive sites. https://doi.org/10.1101/2020.06.26.172718

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