title: Set1 and MLL1/2 Target Distinct Sets of Functionally Different Genomic Loci In Vivo.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Duncan
authors.affiliation: Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors.forename: Alex D
authors.initials: AD
authors.lastname: Chitsazan
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Chris W
authors.initials: CW
authors.lastname: Seidel
authors.affiliation: Howard Hughes Medical Institute; Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sánchez Alvarado
mesh_terms: D000818:Animals; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila; D023281:Genomics; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010986:Platyhelminths
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; C497422:KMT2A protein, human; C120898:KMT2D protein, human; D009363:Neoplasm Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C526068:Setd1A protein, human