RUNX1 regulates transcription of genes involved in differentiation of HSCs

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R-HSA-8939236
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Pathway
Species
Homo sapiens
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The RUNX1:CBFB complex regulates transcription of the SPI1 (PU.1) gene, involved in differentiation of hematopoietic stem cells (HSCs). RUNX1 recruits histone methyltransferase KMT2A (MLL) to the SPI1 gene locus, leading to generation of the activating H3K4Me3 mark on nucleosomes associated with the SPI1 promoter and the upstream regulatory element (Huang et al. 2011). SPI1 transactivation represses self-renewal and proliferation of HSCs (Fukuchi et al. 2008) and is needed for commitment of HSCs to specific hematopoietic lineages (Imperato et al. 2015).
As a component of the TAL1 transcription factor complex, involved in acute T cell lymphoblastic leukemia (T-ALL), RUNX1 can promote growth and inhibit apoptosis of hematopoietic stem cells by stimulating transcription of the MYB gene and possibly the TRIB2 gene (Sanda et al. 2012, Mansour et al. 2014).

Literature References
PubMed ID Title Journal Year
22897851 Core transcriptional regulatory circuit controlled by the TAL1 complex in human T cell acute lymphoblastic leukemia

Sanda, T, Lawton, LN, Barrasa, MI, Fan, ZP, Kohlhammer, H, Gutierrez, A, Ma, W, Tatarek, J, Ahn, Y, Kelliher, MA, Jamieson, CH, Staudt, LM, Young, RA, Look, AT

Cancer Cell 2012
25394790 Oncogene regulation. An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element

Mansour, MR, Abraham, BJ, Anders, L, Berezovskaya, A, Gutierrez, A, Durbin, AD, Etchin, J, Lawton, L, Sallan, SE, Silverman, LB, Loh, ML, Hunger, SP, Sanda, T, Young, RA, Look, AT

Science 2014
25749719 The RUNX1-PU.1 axis in the control of hematopoiesis

Imperato, MR, Cauchy, P, Obier, N, Bonifer, C

Int. J. Hematol. 2015
22012064 The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations

Huang, G, Zhao, X, Wang, L, Elf, S, Xu, H, Zhao, X, Sashida, G, Zhang, Y, Liu, Y, Lee, J, Menendez, S, Yang, Y, Yan, X, Zhang, P, Tenen, DG, Osato, M, Hsieh, JJ, Nimer, SD

Blood 2011
18787208 Activation of CCAAT/enhancer-binding protein alpha or PU.1 in hematopoietic stem cells leads to their reduced self-renewal and proliferation

Fukuchi, Y, Ito, M, Shibata, F, Kitamura, T, Nakajima, H

Stem Cells 2008
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