In vivo deletion of the cebpa +37 kb enhancer markedly reduces cebpa mRNA in myeloid progenitors but not in non- hematopoietic tissues to impair granulopoiesis

PLoS ONE

Volumn 11, Issue 3, 2016, Pages

  Guo, Hong ^a   Cooper, Stacy ^a   Friedman, Alan D ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; EARLY GROWTH RESPONSE FACTOR 1; INTERLEUKIN 3; KRUPPEL LIKE FACTOR 4; MESSENGER RNA; TRANSCRIPTION FACTOR PU 1; CCAAT ENHANCER BINDING PROTEIN; CEBPA PROTEIN, MOUSE; DNA BINDING PROTEIN; EGR1 PROTEIN, MOUSE; GFI1 PROTEIN, MOUSE; KRUPPEL LIKE FACTOR; ONCOPROTEIN; PROTO-ONCOGENE PROTEIN SPI-1; TRANSACTIVATOR PROTEIN; TRANSCRIPTION FACTOR;

ADIPOSE TISSUE; ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CEBPA GENE; CELL CYCLE PROGRESSION; CELL LINEAGE; CELL MATURATION; COLONY FORMING UNIT; CONTROLLED STUDY; EGR1 GENE; EMBRYO; ENHANCER REGION; FEMALE; FETUS; FLUORESCENCE ACTIVATED CELL SORTING; GENE; GENE DELETION; GENE EXPRESSION; GFI1 GENE; GRANULOCYTE PRECURSOR; GRANULOPOIESIS; HEMATOPOIETIC STEM CELL; HEMATOPOIETIC TISSUE; IN VITRO STUDY; IN VIVO STUDY; INTESTINE; KIDNEY; KLF4 GENE; LIVER; LOXP GENE; LUNG; MONOCYTE MACROPHAGE PRECURSOR CELL; MOUSE; MUSCLE; MYELOID PROGENITOR CELL; NEUTROPHIL; NEWBORN; NONHUMAN; PRE B LYMPHOCYTE; PROGENY; PU 1 GENE; STEM CELL EXPANSION; ANIMAL; C57BL MOUSE; CELL LINE; CYTOLOGY; DEFICIENCY; GENE EXPRESSION REGULATION; GENETICS; GRANULOCYTE; LYMPHOPOIESIS; METABOLISM; MOLECULAR GENETICS; MONOCYTE; MYELOPOIESIS; NUCLEOTIDE SEQUENCE; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE;

ANIMALS; BASE SEQUENCE; CCAAT-ENHANCER-BINDING PROTEINS; CELL LINE; CELL LINEAGE; DNA-BINDING PROTEINS; EARLY GROWTH RESPONSE PROTEIN 1; ENHANCER ELEMENTS, GENETIC; FEMALE; GENE EXPRESSION REGULATION; GRANULOCYTES; KRUPPEL-LIKE TRANSCRIPTION FACTORS; LYMPHOPOIESIS; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; MONOCYTES; MYELOID PROGENITOR CELLS; MYELOPOIESIS; PROTO-ONCOGENE PROTEINS; RNA, MESSENGER; SEQUENCE DELETION; SIGNAL TRANSDUCTION; TRANS-ACTIVATORS; TRANSCRIPTION FACTORS;

EID: 84961282401     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0150809     Document Type: Article

References (51)

1. Scott LM, Civin CI, Rorth P, Friedman AD. A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells. Blood 1992; 80: 1725-1735. PMID: 1391942
2. Iwasaki H, Mizuno S, Arinobu Y, Ozawa H, Mori Y, Shigematsu H, et al. The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages. Genes Dev. 2006; 20: 3010-3021. PMID: 17079688
3. Zhang P, Iwasaki-Arai J, Iwasaki H, Fenyus ML, Dayaram T, Owens BM, et al. Enhancement of hematopoietic stem cell repopulating capacity and self-renewal in the absence of the transcription factor C/EBPα. Immunity 2004; 21: 853-863. PMID: 15589173
4. Ma O, Hong S, Guo H, Ghiaur G, Friedman AD. Granulopoiesis requires increased C/EBPα compared to monopoiesis, correlated with elevated Cebpa in immature G-CSF receptor versus M-CSF receptor expressing cells. PLoS One 2014; 9: E95784. doi: 10.1371/journal.pone.0095784 PMID: 24752325
5. Friedman AD. C/EBPα in normal and malignant myelopoiesis. Int J Hematol. 2015; 101: 330-341. doi: 10.1007/s12185-015-1764-6 PMID: 25753223
6. Christy RJ, Kaestner KH, Geiman DE, Lane MD. CCAAT/enhancer binding protein gene promoter: Binding of nuclear factors during differentiation of 3T3-L1 preadipocytes. Proc Natl Acad Sci USA 1991; 88: 2593-2597. PMID: 2006196
7. Guo H, Ma O, Speck NA, Friedman AD. Runx1 deletion or dominant inhibition reduces Cebpa transcription via conserved promoter and distal enhancer sites to favor monopoiesis over granulopoiesis. Blood 2012; 119: 4408-4418. doi: 10.1182/blood-2011-12-397091 PMID: 22451420
8. Guo H, Ma O, Friedman AD. The Cebpa +37 kb enhancer directs transgene expression to myeloid progenitors and to long-term hematopoietic stem cells. J Leuk Biol. 2014; 96: 419-426.
9. Wilson NK, Foster SD, Wang X, Knezevic K, Schütte J, Kaimakis P, et al. Combinatorial transcriptional control in blood stem/progenitor cells: Genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell 2010; 7: 532-544. doi: 10.1016/j.stem.2010.07.016 PMID: 20887958
10. Collins C, Wang J, Miao H, Bronstein J, Nawer H, Xu T, et al. C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis. Proc Natl Acad Sci USA 2014; 111: 9899-9904. doi: 10. 1073/pnas.1402238111 PMID: 24958854
11. Cooper S, Guo H, Friedman AD. The +37 kb Cebpa enhancer is critical for Cebpa myeloid gene expression and contains functional sites that bind SCL, GATA2, C/EBPα, PU.1, and additional Ets factors. PLoS One 2015; 10: E0126385. doi: 10.1371/journal.pone.0126385 PMID: 25938608
12. Sharan SK, Thomason LC, Kuznetsov SG, Court DL. Recombineering: A homologous recombinationbased method of genetic engineering. Nat Prot. 2009; 4: 206-223.
13. Suzow JG, Friedman AD. The murine myeloperoxidase promoter contains multiple functional elements -one element binds a cell type-restricted transcription factor, myeloid nuclear factor 1(MyNF1). Mol Cell Biol. 1993; 13: 2141-2151. PMID: 8384306
14. Ye M, Zhang H, Amabile G, Yang H, Staber PB, Zhang P, et al. C/EBPα controls acquisition and maintenance of adult haematopoietic stem cell quiescence. Nat Cell Biol. 2013; 15: 385-394. doi: 10.1038/ncb2698 PMID: 23502316
15. Hasemann MS, Lauridsen FK, Waage J, Jakobsen JS, Frank AK, Schuster MB, et al. C/EBPα is required for long-term self-renewal and lineage priming of hematopoietic stem cells and for the maintenance of epigenetic configurations in multipotent progenitors. PLoS Genet. 2014; 10: E1004079. doi: 10.1371/journal.pgen.1004079 PMID: 24415956
16. Schwenk F, Baron U, Rajewsky K. A cre-transgenic mouse strain for ubiquitous deletion of loxP-flanked segments including deletion in germ cells. Nucl. Acids Res. 1995; 23: 5080-5081. PMID: 8559668
17. Birkenmeier EH, Gwynn B, Howard S, Jerry J, Gordon JI, Landschulz WH, et al. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev. 1989; 3: 1146-1156. PMID: 2792758
18. Flodby P, Barlow C, Kylefjord H, Ahrlund-Richter L, Xanthopoulos KG. Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein ?. J Biol Chem. 1996; 271: 24753-24760. PMID: 8798745
19. Wang N, Finegold MJ, Bradley A, Ou CN, Abdelsayed SV, Wilde MD, et al. Impaired energy homeostasis in C/EBPα knockout mice. Science 1995; 269: 1108-1112. PMID: 7652557
20. Kummalue T, Friedman AD. Cross-talk between regulators of myeloid development: C/EBPα binds and activates the promoter of the PU.1 gene. J Leukoc Biol. 2003; 74: 464-470. PMID: 12949251
21. Yeamans C, Wang D, Paz-Priel I, Torbett BE, Tenen DG, Friedman AD. C/EBPα binds and activates the PU.1 distal enhancer to induce monocyte lineage commitment. Blood 2007; 110: 3136-3142. PMID: 17671233
22. Hock H, Hamblen MJ, Rooke HM, Traver D, Bronson RT, Cameron S, et al. Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation. Immunity 2003; 18: 109-120. PMID: 12530980
23. Krishnaraju K, Hoffman B, Liebermann DA. Early growth response gene 1 stimulates development of hematopoietic progenitor cells along the macrophage lineage at the expense of the granulocyte and erythroid lineages. Blood 2001; 97: 1298-1305. PMID: 11222373
24. Kurotaki D, Osato N, Nishiyama A, Yamamoto M, Ban T, Sato H, et al. Essential role of the IRF8-KLF4 transcription factor cascade in murine monocyte differentiation. Blood 2013; 121: 1839-1849. doi: 10.1182/blood-2012-06-437863 PMID: 23319570
25. Tamura T, Kurotaki D, Koizumi S. Regulation of myelopoiesis by the transcription factor IRF8. Int J Hematol. 2015; 101: 342-351. doi: 10.1007/s12185-015-1761-9 PMID: 25749660
26. Paul F, Arkin Y, Giladi A, Jaitin DA, Kenigsberg E, Keren-Shaul H, et al. Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell 2015; 163: 1663-1677. doi: 10.1016/j.cell.2015. 11.013 PMID: 26627738
27. Jones LC, Lin ML, Chen SS, Krug U, Hofmann WK, Lee S, et al. Expression of C/EBPα from the C/ebpa gene locus is sufficient for normal hematopoiesis in vivo. Blood 2002; 99: 2032-2036. PMID: 11877276
28. Hirai H, Zhang P, Dayaram T, Hetherington CJ, Mizuno S, Imanishi J, et al. C/EBPα is required for 'emergency' granulopoiesis. Nat Immunol. 2006; 7: 732-739. PMID: 16751774
29. Alberich-Jordà M, Wouters B, Balastik M, Shapiro-Koss C, Zhang H, Di Ruscio A, et al. C/EBP deregulation results in differentiation arrest in acute myeloid leukemia. J Clin Invest. 2012; 122: 4490-4504. doi: 10.1172/JCI65102 PMID: 23160200
30. Zhang DE, Zhang P, Wang ND, Hetherington CJ, Darlington GJ, Tenen DG. Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein α-deficient mice. Proc Natl Acad Sci USA 1997; 94: 569-574. PMID: 9012825
31. Heath V, Suh HC, Holman M, Renn K, Gooya JM, Parkin S, et al. C/EBPα deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo. Blood 2004; 104: 1639-1647. PMID: 15073037
32. Zhang P, Nelson E, Radomska HS, Iwasaki-Arai J, Akashi K, Friedman AD et al. Induction of granulocytic differentiation by 2 pathways. Blood 2002; 99: 4406-4412. PMID: 12036869
33. Wang X, Scott E, Sawyers CL, and Friedman AD. C/EBP bypasses G-CSF signals to rapidly induce PU.1 gene expression, stimulate granulocytic differentiation, and limit proliferation in 32D cl3 myeloblasts. Blood 1999; 94: 560-571. PMID: 10397723
34. Porse BT, Pedersen TA, Xu X, Lindberg B, Wewer UM, Friis-Hansen L, et al. E2F repression by C/EBP is required for adipogenesis and granulopoiesis in vivo. Cell 2001; 107: 247-258. PMID: 11672531
35. Wang QF, Cleaves R, Kummalue T, Nerlov C, Friedman AD. Cell cycle inhibition mediated by the outer surface of the C/EBPα basic region is required but not sufficient for granulopoiesis. Oncogene 2003; 22: 2548-2557. PMID: 12730669
36. Paz-Priel I, Cai DH, Wang D, Kowalski J, Blackford A, Liu H, et al. C/EBPα and C/EBPα myeloid oncoproteins induce Bcl-2 via interaction of their basic regions with NF-?B p50. Mol. Cancer Res. 2005; 3: 585-596.
37. Johansen LM, Iwama A, Lodie TA, Sasaki K, Felsher DW, Golub TR, et al. c-Myc is a critical target for C/EBPα in granulopoiesis. Mol Cell Biol. 2001; 21: 3789-3806. PMID: 11340171
38. Umek RM, Friedman AD, McKnight SL. CCAAT-enhancer binding protein: A component of a differentiation switch. Science 1991; 251: 288-292. PMID: 1987644
39. Suh HC, Gooya J, Renn K, Friedman AD, Johnson PF, Keller JR. C/EBPα determines hematopoietic cell fate in multipotential progenitor cells by inhibiting erythroid differentiation and inducing myeloid differentiation. Blood 2006; 107: 4308-4316. PMID: 16469877
40. Cai DH, Wang D, Keefer J, Yeamans C, Hensley K, Friedman AD. C/EBPα:AP-1 leucine zipper heterodimers bind novel DNA elements, activate the PU.1 promoter, and direct monocyte lineage commitment more potently than C/EBPα homodimers or AP-1. Oncogene 2008; 27: 2772-2779. PMID: 18026136
41. Hong SH, Skaist AM, Wheelan SJ, Friedman AD. AP-1 protein induction during monopoiesis favors C/EBP:AP-1 heterodimers over C/EBP homodimerization and stimulates FosB transcription. J Leuk Biol. 2011; 90: 643-651.
42. Montecino-Rodriguez E, Leathers H, Dorshkind K. Bipotential B-macrophage progenitors are present in adult bone marrow. Nat Immunol. 2001; 2: 83-88. PMID: 11135583
43. Balciunaite G, Ceredig R, Massa S, Rolink AG. A B220+ CD117+ CD19-hematopoietic progenitor with potent lymphoid and myeloid developmental potential. Eur J Immunol. 2005; 35: 2019-2030. PMID: 15971276
44. Richie Ehrlich LI, Serwold T, Weissman IL. In vitro assays misrepresent in vivo lineage potentials of murine lymphoid progenitors. Blood 2011; 117: 2618-2624. doi: 10.1182/blood-2010-05-287102 PMID: 21163922
45. Xie H, Ye M, Feng R, Graf T. Stepwise reprogramming of B cells into macrophages. Cell 2004; 117: 663-676. PMID: 15163413
46. Paz-Priel I, Ghosal AK, Kowalski J, and Friedman AD. C/EBPα or C/EBPα oncoproteins regulate the intrinsic and extrinsic apoptotic pathways by direct interaction with NF-B p50 bound to the bcl-2 and FLIP gene promoters. Leukemia 2009; 23: 365-374. doi: 10.1038/leu.2008.297 PMID: 18987666
47. Wagner K, Zhang P, Rosenbauer F, Drescher B, Kobayashi S, Radomska HS, et al. Absence of the transcription factor CCAAT enhancer binding protein ? results in loss of myeloid identity in bcr/ablinduced malignancy. Proc Natl Acad Sci USA 2006; 103: 6338-6343. PMID: 16606850
48. Kirstetter P, Schuster MB, Bereshchenko O, Moore S, Dvinge H, Kurz E, et al. Modeling of C/EBPα mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer Cell 2008; 13: 299-310. doi: 10.1016/j.ccr.2008.02.008 PMID: 18394553
49. Ye M, Zhang H, Yang H, Koche R, Staber PB, Cusan M, et al. Hematopoietic differentiation is required for initiation of acute myeloid leukemia. Cell Stem Cell 2015; 17: 611-623. doi: 10.1016/j.stem.2015. 08.011 PMID: 26412561
50. Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult De novo acute myeloid leukemia. New Engl J Med. 2013; 368: 2059-2074. doi: 10.1056/NEJMoa1301689 PMID: 23634996
51. Ptasinska A, Assi SA, Mannari D, James SR, Williamson D, Dunne J, et al. Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia 2012; 26:1829-1841. doi: 10.1038/leu.2012.49 PMID: 22343733