The Trithorax-related Set1 H3K4 methyltransferases are conserved from yeast to human. In yeast loss of Set1 causes pleiotropic effects but is compatible with life. In contrast, both mammalian Set1 orthologs: SETD1A and SETD1B are essential for embryonic development, however they have distinct functions. SETD1A is required shortly after epiblast formation whereas SETD1B becomes indispensible during early organogenesis. In adult mice both SETD1A and SETD1B regulate hematopoiesis differently: SETD1A is required for the establishment of definitive hematopoiesis whereas SETD1B is important for the maintenance of long-term hematopoietic stem cells. Both are implicated in different diseases with accumulating evidence for the association of SETD1A variants in neurological disorders and SETD1B variants with cancer. Why the two paralogs cannot or only partially compensate for the loss of each other is part of the puzzle that we try to sort out in this review.

中文翻译：

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SETD1A和SETD1B在发育和疾病中的作用。

Trithorax相关的Set1 H3K4甲基转移酶从酵母到人都是保守的。在酵母中，Set1的缺失会引起多效性效应，但与生命相容。相反，哺乳动物Set1直系同源物：SETD1A和SETD1B对于胚胎发育必不可少，但是它们具有独特的功能。在成胚细胞形成后不久需要SETD1A，而在早期器官发生过程中SETD1B变得必不可少。在成年小鼠中，SETD1A和SETD1B对造血功能的调节不同：SETD1A是确定性造血功能的建立所必需的，而SETD1B对于长期造血干细胞的维持很重要。两者都与不同的疾病有关，并且积累了神经系统疾病中SETD1A变体与SETD1B变体与癌症相关的证据。