Howard Hughes Medical Institute.
Department of Biology, University of Oregon, Eugene, OR 97403, USA.
Cell Rep. 2015 Dec 29;13(12):2741-55. doi: 10.1016/j.celrep.2015.11.059. Epub 2015 Dec 17.
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.
组蛋白 H3 赖氨酸 4 三甲基化（H3K4me3）与活跃和静止的基因组位点都有关联，但关于其在体内的功能作用仍有许多问题亟待解决。我们鉴定了两种 H3K4 甲基转移酶（Set1 和 MLL1/2）在扁形动物秀丽隐杆线虫的干细胞和分化组织中的功能基因组靶标。我们发现，尽管它们有共同的底物，但这两种酶在体内靶向不同的基因组位点，这可以通过每种酶在染色质模板上留下的模式来区分，即 H3K4me3 峰的宽度。虽然 Set1 的靶标主要与干细胞群体的维持有关，但 MLL1/2 的靶标则特异性富集了参与纤毛发生的基因。这些数据不仅证实了染色质调控对扁形动物干细胞功能至关重要，还为体内 H3K4me3 甲基转移酶的胚胎后功能特异性提供了证据。
