The role of SETD1A and SETD1B in development and disease

Postnatal SETD1B is essential for learning and the regulation of neuronal plasticity genes

“…However, specificity likely depends on the cellular context and care has to be taken when interpreting the different in vitro and in vivo data. Nevertheless, our data are in line with studies showing that SETD1B preferentially mediates H3K4-trimethylation when compared to the other KMTs such as KMT2A and KMT2B that are believed to mediate monoand di-methylation with comparatively low H3K4 tri-methylation activity (Wu et al, 2008) (Lee & Skalnik, 2008) (Shinsky et al, 2015) (Bochyńska et al, 2018;Rao RC, 2015) (Kranz & Anastassiadis, 2020).…”

“…Interestingly, mice heterozygous for Setd1a, the close homologue to Setd1b that is genetically linked to schizophrenia, show no impairment in the water maze task but rather exhibit impaired working memory and schizophrenia-like phenotypes (Mukai et al, 2019). Distinct roles for Setd1b and Setd1a are also reported for other cellular system (Bledau et al, 2014) (Arndt et al, 2018;Brici et al, 2017; 10 Kranz & Anastassiadis, 2020;Schmidt et al, 2018). These data suggest that the different H3K4 KMTs, and at least Kmt2a, Kmt2b, Setd1a and Setd1b, likely serve distinct functions in the postnatal brain.…”

“…The fact that loss of either Kmt2a, Kmt2b or Setd1b leads to distinct changes in neuronal gene-expression might also be due to the specific subunit compositions of the KMT complexes. (Kranz & Anastassiadis, 2020). While all H3K4 KMTs are believed to interact with a number of core subunits (Kranz & Anastassiadis, 2020), data from other cell types than neurons show that KMT2A and KMT2B can bind the transcriptional regulator multiple endocrine neoplasia type 1 (Menin) (Hughes et al, 2004).…”

“…(Kranz & Anastassiadis, 2020). While all H3K4 KMTs are believed to interact with a number of core subunits (Kranz & Anastassiadis, 2020), data from other cell types than neurons show that KMT2A and KMT2B can bind the transcriptional regulator multiple endocrine neoplasia type 1 (Menin) (Hughes et al, 2004). In contrast, SETD1B was shown to interact with CXXC finger protein 1 (CFP1) and WDR82 which binds to RNA-polymerase II.…”

Setd1a Plays Pivotal Roles for the Survival and Proliferation of Retinal Progenitors via Histone Modifications of Uhrf1

“…Abnormalities in the H3K4 methyltransferases MLL1, MLL3, and MLL4 have been shown to result in cancer and hematopoietic malignancies. 55 In addition, in MLL-AF9 leukemia, SETD1A is required for cell survival and leukemia progression in vitro as well as in vivo . 19 It should be noted that we performed this study in retinal explants, which has limitation to reproduce all the biological phenomena occur in in vivo because additional stress to the retina by making the explant culture may affect the results.…”