Target Regulator(s) Information (Transcription Factor)

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Target General Information
The Transcription Factors (TFs) Regulating This Target
References
Target General Information  Top
Target ID T98913 Target Info
Target Name Granulocyte colony-stimulating factor receptor (G-CSF-R)
Synonyms c-fms; GCSFR; GCSF receptor; G-CSF receptor; Fms proto-oncogene; CD114
Target Type Successful Target
Gene Name CSF3R
Biochemical Class Cytokine receptor
UniProt ID
CSF3R_HUMAN
The Transcription Factors (TFs) Regulating This Target  Top
TF Name C/EBP alpha (CEBPA) homodimer
Classification Superclass Basic Domains
Class Leucine zipper factors (bZIP)
Family C/EBP-like factors
Regulation Type Increase
Regulation Mechanism There are two regions that are important for GCSFR promoter activity. One region, located at bp -49, contains a GCAAT site that specifically binds the C/EBP alpha transcription factor in myeloid nuclear extracts. Mutation of this site prevents C/EBP alpha binding and reduces promoter activity by 60%. The other functionally important region of GCSFR promoter is in the 5' untranslated region, at bp +36 and +43, where there are two sites for the ets family member PU.1. [1]
Evidence Score (E-score) 2 +
1 Electrophoretic Mobility Shift Assay [1]
2 Electrophoretic Mobility Shift Assay [2]
UniProt ID
CEBPA_HUMAN
Sequence
MESADFYEAEPRPPMSSHLQSPPHAPSSAAFGFPRGAGPAQPPAPPAAPEPLGGICEHET
SIDISAYIDPAAFNDEFLADLFQHSRQQEKAKAAVGPTGGGGGGDFDYPGAPAGPGGAVM
PGGAHGPPPGYGCAAAGYLDGRLEPLYERVGAPALRPLVIKQEPREEDEAKQLALAGLFP
YQPPPPPPPSHPHPHPPPAHLAAPHLQFQIAHCGQTTMHLQPGHPTPPPTPVPSPHPAPA
LGAAGLPGPGSALKGLGAAHPDLRASGGSGAGKAKKSVDKNSNEYRVRRERNNIAVRKSR
DKAKQRNVETQQKVLELTSDNDRLRKRVEQLSRELDTLRGIFRQLPESSLVKAMGNCA
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Apolipoproteins [+] 3 Apolipoproteins Co-regulated By This TF +
1 Apolipoprotein A-II (APOA2) Literature-reported Target Target Info [3]
2 Apolipoprotein B-100 (APOB) Clinical trial Target Target Info [4]
3 Apolipoprotein E (APOE) Clinical trial Target Target Info [5]
Calcium-binding proteins [+] 1 Calcium-binding proteins Co-regulated By This TF +
1 Calgranulin B (S100A9) Clinical trial Target Target Info [6]
Coagulation factors [+] 1 Coagulation factors Co-regulated By This TF +
1 Coagulation factor VIII (F8) Successful Target Target Info [7]
Cytokines / Cytokine receptors [+] 1 Cytokines / Cytokine receptors Co-regulated By This TF +
1 Granulocyte colony-stimulating factor receptor (G-CSF-R) Successful Target Target Info [1]
Glycoproteins [+] 1 Glycoproteins Co-regulated By This TF +
1 Cholesteryl ester transfer protein (CETP) Clinical trial Target Target Info [8]
Integrins [+] 1 Integrins Co-regulated By This TF +
1 Integrin alpha-2 (ITGA2) Clinical trial Target Target Info [9]
Lipoprotein receptors [+] 1 Lipoprotein receptors Co-regulated By This TF +
1 Low-density lipoprotein receptor (LDL-R) Successful Target Target Info [10]
Oxidoreductases [+] 1 Oxidoreductases Co-regulated By This TF +
1 Entamoeba Alcohol dehydrogenase 2 (Entamo ADH2) Literature-reported Target Target Info [11]
Peptidases [+] 1 Peptidases Co-regulated By This TF +
1 Coagulation factor IX (F9) Successful Target Target Info [12]
Somatotropin / Prolactins [+] 1 Somatotropin / Prolactins Co-regulated By This TF +
1 Prolactin (PRL) Discontinued Target Target Info [13]
Transferrins [+] 1 Transferrins Co-regulated By This TF +
1 Transferrin (TF) Clinical trial Target Target Info [14]
TF Name PU.1 proto-oncogene (SPI1)
Classification Superclass Helix-turn-helix
Class Tryptophan clusters
Family Ets-type
Regulation Type Increase
Regulation Mechanism There are two regions that are important for GCSFR promoter activity. One region, located at bp -49, contains a GCAAT site that specifically binds the C/EBP alpha transcription factor in myeloid nuclear extracts. Mutation of this site prevents C/EBP alpha binding and reduces promoter activity by 60%. The other functionally important region of GCSFR promoter is in the 5' untranslated region, at bp +36 and +43, where there are two sites for the ets family member PU.1. [1]
Evidence Score (E-score) 1 +
1 Electrophoretic Mobility Shift Assay [1]
UniProt ID
SPI1_HUMAN
Sequence
MLQACKMEGFPLVPPPSEDLVPYDTDLYQRQTHEYYPYLSSDGESHSDHYWDFHPHHVHS
EFESFAENNFTELQSVQPPQLQQLYRHMELEQMHVLDTPMVPPHPSLGHQVSYLPRMCLQ
YPSLSPAQPSSDEEEGERQSPPLEVSDGEADGLEPGPGLLPGETGSKKKIRLYQFLLDLL
RSGDMKDSIWWVDKDKGTFQFSSKHKEALAHRWGIQKGNRKKMTYQKMARALRNYGKTGE
VKKVKKKLTYQFSGEVLGRGGLAERRHPPH
The Genes (Co-regulated by This TF) Grouped Based on Their Biochemical Classes
Cytokines / Cytokine receptors [+] 4 Cytokines / Cytokine receptors Co-regulated By This TF +
1 CD40L receptor (CD40) Clinical trial Target Target Info [15]
2 Granulocyte colony-stimulating factor receptor (G-CSF-R) Successful Target Target Info [1]
3 Interleukin-1 beta (IL1B) Successful Target Target Info [16]
4 Interleukin-12 beta (IL12B) Successful Target Target Info [17]
Integrins [+] 1 Integrins Co-regulated By This TF +
1 Integrin beta-2 (ITGB2) Clinical trial Target Target Info [18]
References  Top
REF 1 PU.1 (Spi-1) and C/EBP alpha regulate the granulocyte colony-stimulating factor receptor promoter in myeloid cells. Blood. 1996 Aug 15;88(4):1234-47.
REF 2 Essential role of C/EBPalpha in G-CSF-induced transcriptional activation and chromatin modification of myeloid-specific genes. Genes Cells. 2008 Apr;13(4):313-27.
REF 3 Regulation of the human ApoA-II gene by the synergistic action of factors binding to the proximal and distal regulatory elements. J Biol Chem. 1991 Dec 25;266(36):24460-70.
REF 4 Identification and characterization of a 315-base pair enhancer, located more than 55 kilobases 5' of the apolipoprotein B gene, that confers expression in the intestine. J Biol Chem. 2000 Aug 25;275(34):26637-48.
REF 5 Structure of the hepatic control region of the human apolipoprotein E/C-I gene locus. J Biol Chem. 1995 Sep 22;270(38):22577-85.
REF 6 Transcriptional regulation by C/EBP alpha and -beta in the expression of the gene for the MRP14 myeloid calcium binding protein. Cell Struct Funct. 1998 Jun;23(3):109-18.
REF 7 Role of the liver-enriched transcription factor hepatocyte nuclear factor 1 in transcriptional regulation of the factor V111 gene. Mol Cell Biol. 1996 May;16(5):1936-45.
REF 8 The CCAAT/enhancer-binding protein trans-activates the human cholesteryl ester transfer protein gene promoter. J Biol Chem. 1992 Nov 5;267(31):22336-9.
REF 9 The alpha2 and alpha5 integrin genes: identification of transcription factors that regulate promoter activity in epidermal keratinocytes. FEBS Lett. 2000 Jun 2;474(2-3):201-7.
REF 10 Identification of a novel sterol-independent regulatory element in the human low density lipoprotein receptor promoter. J Biol Chem. 2000 Feb 18;275(7):5214-21.
REF 11 The role of CCAAT/enhancer-binding protein in the differential transcriptional regulation of a family of human liver alcohol dehydrogenase genes. J Biol Chem. 1991 Jun 25;266(18):11594-603.
REF 12 Binding of the Ets factor GA-binding protein to an upstream site in the factor IX promoter is a critical event in transactivation. Mol Cell Biol. 1996 May;16(5):1929-35.
REF 13 CCAAT/enhancer-binding proteins are mediators in the protein kinase A-dependent activation of the decidual prolactin promoter. J Biol Chem. 1999 Aug 27;274(35):24808-18.
REF 14 A different combination of transcription factors modulates the expression of the human transferrin promoter in liver and Sertoli cells. J Biol Chem. 1993 Nov 5;268(31):23399-408.
REF 15 IL-4-activated STAT-6 inhibits IFN-gamma-induced CD40 gene expression in macrophages/microglia. J Immunol. 2000 Dec 1;165(11):6235-43.
REF 16 Monocyte expression of the human prointerleukin 1 beta gene (IL1B) is dependent on promoter sequences which bind the hematopoietic transcription fa... Mol Cell Biol. 1995 Jan;15(1):58-68.
REF 17 Identification and characterization of a novel Ets-2-related nuclear complex implicated in the activation of the human interleukin-12 p40 gene prom... J Biol Chem. 1997 Apr 18;272(16):10389-95.
REF 18 CD18 (beta 2 leukocyte integrin) promoter requires PU.1 transcription factor for myeloid activity. Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):801-5.

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