Distal regulation of c-myb expression during IL-6-induced differentiation in murine myeloid progenitor M1 cells.
The c-Myb transcription factor is a major regulator that controls differentiation and proliferation of hematopoietic progenitor cells, which is frequently deregulated in hematological diseases, such as lymphoma and leukemia. Understanding of the mechanisms regulating the transcription of c-myb gene is challenging as it lacks a typical promoter and multiple factors are involved. Our previous studies identified some distal regulatory elements in the upstream regions of c-myb gene in murine myeloid progenitor M1 cells, but the detailed mechanisms still remain unclear. In the present study, we found that a cell differentiation-related DNase1 hypersensitive site is located at a -28k region upstream of c-myb gene and that transcription factors Hoxa9, Meis1 and PU.1 bind to the -28k region. Circular chromosome conformation capture (4C) assay confirmed the interaction between the -28k region and the c-myb promoter, which is supported by the enrichment of CTCF and Cohesin. Our analysis also points to a critical role for Hoxa9 and PU.1 in distal regulation of c-myb expression in murine myeloid cells and cell differentiation. Overexpression of Hoxa9 disrupted the IL-6-induced differentiation of M1 cells and upregulated c-myb expression through binding of the -28k region. Taken together, our results provide an evidence for critical role of the -28k region in distal regulatory mechanism for c-myb gene expression during differentiation of myeloid progenitor M1 cells.
Key Laboratory of Aquacultural Resources and Utilization, Ministry of Education, College of Fishery and Life Science, Shanghai Ocean University, No.999 Huchenghuan Road, Pudong New District, Shanghai 201306, China.
Junfang
J
Zhang
Key Laboratory of Aquacultural Resources and Utilization, Ministry of Education, College of Fishery and Life Science, Shanghai Ocean University, No.999 Huchenghuan Road, Pudong New District, Shanghai 201306, China.
Bingshe
B
Han
Key Laboratory of Aquacultural Resources and Utilization, Ministry of Education, College of Fishery and Life Science, Shanghai Ocean University, No.999 Huchenghuan Road, Pudong New District, Shanghai 201306, China.
Xiaoxia
X
Li
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Juraj
J
Bies
Key Laboratory of Aquacultural Resources and Utilization, Ministry of Education, College of Fishery and Life Science, Shanghai Ocean University, No.999 Huchenghuan Road, Pudong New District, Shanghai 201306, China.
Penglei
P
Jiang
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Richard P
RP
Koller
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Linda
L
Wolff
D000818:Animals; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000276:immunology; D003850:Deoxyribonuclease I / Q000235:genetics / Q000276:immunology; D015973:Gene Expression Regulation, Leukemic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000276:immunology; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D023461:Myeloid Progenitor Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000276:immunology; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics* / Q000276:immunology; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics* / Q000276:immunology; D000097722:Cohesins; D000099232:Proto-Oncogene Protein Spi-1
D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003850:Deoxyribonuclease I; D018398:Homeodomain Proteins; D015850:Interleukin-6; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D012097:Repressor Proteins; D015534:Trans-Activators; D000097722:Cohesins; D000099232:Proto-Oncogene Protein Spi-1; C000619698:Ctcf protein, mouse; C000616392:Meis1 protein, mouse; C097899:homeobox protein HOXA9; C577686:interleukin-6, mouse