Set1 and MLL1/2 target distinct sets of functionally different genomic loci in vivo

Elizabeth M. Duncan, Alex D. Chitsazan, Chris W. Seidel, Alejandro Sánchez Alvarado

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Histone H3 lysine 4 trimethylation (H3K4me3) is known to correlate with both active and poised genomic loci, yet many questions remain regarding its functional roles in vivo. We identify functional genomic targets of two H3K4 methyltransferases, Set1 and MLL1/2, in both the stem cells and differentiated tissue of the planarian flatworm Schmidtea mediterranea. We show that, despite their common substrate, these enzymes target distinct genomic loci in vivo, which are distinguishable by the pattern each enzyme leaves on the chromatin template, i.e., the breadth of the H3K4me3 peak. Whereas Set1 targets are largely associated with the maintenance of the stem cell population, MLL1/2 targets are specifically enriched for genes involved in ciliogenesis. These data not only confirm that chromatin regulation is fundamental to planarian stem cell function but also provide evidence for post-embryonic functional specificity of H3K4me3 methyltransferases in vivo.

Original languageEnglish
Pages (from-to)2741-2755
Number of pages15
JournalCell Reports
Issue number12
StatePublished - 2015

Bibliographical note

Funding Information:
We thank all members of the A.S.A. laboratory for discussion and advice, K. Gotting for assistance in analysis, A. Ruthenburg for input on ChIP experiments, and L.A. Banaszynski and C.D. Allis for valuable input on the manuscript. We also thank the Cytometry, Molecular Biology, Histology and Tissue Culture core facilities at the Stowers Institute for Medical Research. E.M.D. is a Damon Runyon HHMI fellow. A.S.A. is a Howard Hughes Medical Institute and Stowers Institute for Medical Research investigator. This work was supported by NIH grant R37GM057260.

Publisher Copyright:
© 2015 The Authors.

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)


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