9ynz

Structural highlights

Disease

SPI1_HUMAN Autosomal agammaglobulinemia. The disease is caused by variants affecting the gene represented in this entry.

Function

SPI1_HUMAN Pioneer transcription factor, which controls hematopoietic cell fate by decompacting stem cell heterochromatin and allowing other transcription factors to enter otherwise inaccessible genomic sites. Once in open chromatin, can directly control gene expression by binding genetic regulatory elements and can also more broadly influence transcription by recruiting transcription factors, such as interferon regulatory factors (IRFs), to otherwise inaccessible genomic regions (PubMed:23658224, PubMed:33951726). Transcriptionally activates genes important for myeloid and lymphoid lineages, such as CSF1R (By similarity). Transcriptional activation from certain promoters, possibly containing low affinity binding sites, is achieved cooperatively with other transcription factors. FCER1A transactivation is achieved in cooperation with GATA1 (By similarity). May be particularly important for the pro- to pre-B cell transition (PubMed:33951726). Binds (via the ETS domain) onto the purine-rich DNA core sequence 5'-GAGGAA-3', also known as the PU-box (PubMed:33951726). In vitro can bind RNA and interfere with pre-mRNA splicing (By similarity).[UniProtKB:P17433][UniProtKB:Q6BDS1]^{[1] [2]}

References

1. ↑ Pham TH, Minderjahn J, Schmidl C, Hoffmeister H, Schmidhofer S, Chen W, Längst G, Benner C, Rehli M. Mechanisms of in vivo binding site selection of the hematopoietic master transcription factor PU.1. Nucleic Acids Res. 2013 Jul;41(13):6391-402. PMID:23658224 doi:10.1093/nar/gkt355
2. ↑ Le Coz C, Nguyen DN, Su C, Nolan BE, Albrecht AV, Xhani S, Sun D, Demaree B, Pillarisetti P, Khanna C, Wright F, Chen PA, Yoon S, Stiegler AL, Maurer K, Garifallou JP, Rymaszewski A, Kroft SH, Olson TS, Seif AE, Wertheim G, Grant SFA, Vo LT, Puck JM, Sullivan KE, Routes JM, Zakharova V, Shcherbina A, Mukhina A, Rudy NL, Hurst ACE, Atkinson TP, Boggon TJ, Hakonarson H, Abate AR, Hajjar J, Nicholas SK, Lupski JR, Verbsky J, Chinn IK, Gonzalez MV, Wells AD, Marson A, Poon GMK, Romberg N. Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. J Exp Med. 2021 Jul 5;218(7):e20201750. PMID:33951726 doi:10.1084/jem.20201750