| Structural highlights
Function
[FOG1_MOUSE] Transcription regulator that plays an essential role in erythroid and megakaryocytic cell differentiation. Essential cofactor that acts via the formation of a heterodimer with transcription factors of the GATA family GATA1, GATA2 and GATA3. Such heterodimer can both activate or repress transcriptional activity, depending on the cell and promoter context. The heterodimer formed with GATA proteins is essential to activate expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, while it represses expression of KLF1. May be involved in regulation of some genes in gonads. May also be involved in cardiac development, in a non-redundant way with ZFPM2/FOG2.[1] [2] [3] [4] [5] [6] [7]
Publication Abstract from PubMed
FOG1 is a transcriptional regulator that acts in concert with the hematopoietic master regulator GATA1 to coordinate the differentiation of platelets and erythrocytes. Despite considerable effort, however, the mechanisms through which FOG1 regulates gene expression are only partially understood. Here we report the discovery of a previously unrecognized domain in FOG1: a PR (PRD-BF1 and RIZ) domain that is distantly related in sequence to the SET domains that are found in many histone methyltransferases. We have used NMR spectroscopy to determine the solution structure of this domain, revealing that the domain shares close structural similarity with SET domains. Titration with S-adenosyl-L-homocysteine, the cofactor product synonymous with SET domain methyltransferase activity, indicated that the FOG PR domain is not, however, likely to function as a methyltransferase in the same fashion. We also sought to define the function of this domain using both pulldown experiments and gel shift assays. However, neither pulldowns from mammalian nuclear extracts nor yeast two-hybrid assays reproducibly revealed binding partners, and we were unable to detect nucleic-acid-binding activity in this domain using our high-diversity Pentaprobe oligonucleotides. Overall, our data demonstrate that FOG1 is a member of the PRDM (PR domain containing proteins, with zinc fingers) family of transcriptional regulators. The function of many PR domains, however, remains somewhat enigmatic for the time being.
The identification and structure of an N-terminal PR domain show that FOG1 is a member of the PRDM family of proteins.,Clifton MK, Westman BJ, Thong SY, O'Connell MR, Webster MW, Shepherd NE, Quinlan KG, Crossley M, Blobel GA, Mackay JP PLoS One. 2014 Aug 27;9(8):e106011. doi: 10.1371/journal.pone.0106011., eCollection 2014. PMID:25162672[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tsang AP, Visvader JE, Turner CA, Fujiwara Y, Yu C, Weiss MJ, Crossley M, Orkin SH. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell. 1997 Jul 11;90(1):109-19. PMID:9230307
- ↑ Tsang AP, Fujiwara Y, Hom DB, Orkin SH. Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes Dev. 1998 Apr 15;12(8):1176-88. PMID:9553047
- ↑ Crispino JD, Lodish MB, MacKay JP, Orkin SH. Use of altered specificity mutants to probe a specific protein-protein interaction in differentiation: the GATA-1:FOG complex. Mol Cell. 1999 Feb;3(2):219-28. PMID:10078204
- ↑ Fox AH, Liew C, Holmes M, Kowalski K, Mackay J, Crossley M. Transcriptional cofactors of the FOG family interact with GATA proteins by means of multiple zinc fingers. EMBO J. 1999 May 17;18(10):2812-22. PMID:10329627 doi:http://dx.doi.org/10.1093/emboj/18.10.2812
- ↑ Katz SG, Cantor AB, Orkin SH. Interaction between FOG-1 and the corepressor C-terminal binding protein is dispensable for normal erythropoiesis in vivo. Mol Cell Biol. 2002 May;22(9):3121-8. PMID:11940669
- ↑ Wang X, Crispino JD, Letting DL, Nakazawa M, Poncz M, Blobel GA. Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: role of Ets transcription factors. EMBO J. 2002 Oct 1;21(19):5225-34. PMID:12356738
- ↑ Katz SG, Williams A, Yang J, Fujiwara Y, Tsang AP, Epstein JA, Orkin SH. Endothelial lineage-mediated loss of the GATA cofactor Friend of GATA 1 impairs cardiac development. Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14030-5. Epub 2003 Nov 12. PMID:14614148 doi:http://dx.doi.org/10.1073/pnas.1936250100
- ↑ Clifton MK, Westman BJ, Thong SY, O'Connell MR, Webster MW, Shepherd NE, Quinlan KG, Crossley M, Blobel GA, Mackay JP. The identification and structure of an N-terminal PR domain show that FOG1 is a member of the PRDM family of proteins. PLoS One. 2014 Aug 27;9(8):e106011. doi: 10.1371/journal.pone.0106011., eCollection 2014. PMID:25162672 doi:http://dx.doi.org/10.1371/journal.pone.0106011
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