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Transcriptional deregulation of oncogenic myocyte enhancer factor 2C in T-cell acute lymphoblastic leukemia
- Source :
- Leukemia & Lymphoma. 52:290-297
- Publication Year :
- 2011
- Publisher :
- Informa UK Limited, 2011.
-
Abstract
- Myocyte enhancer factor 2C (MEF2C) encodes a transcription factor which is ectopically expressed in T-cell acute lymphoblastic leukemia (T-ALL) cell lines, deregulated directly by ectopically expressed homeodomain protein NKX2-5 or by loss of promoter regions via del(5)(q14). Here, we analyzed the MEF2C 5'-region, thus identifying potential regulatory binding sites for GFI1B, basic helix-loop-helix proteins, STAT5, and HOXA9/HOXA10. Chromatin immunoprecipitation and overexpression analyses demonstrated direct activation by GFI1B and LYL1 and inhibition by STAT5. HOXA9/HOXA10 activated expression of NMYC which in turn mediated MEF2C repression, indicating an indirect mode of regulation via NMYC interactor (NMI) and STAT5. Lacking comma: Chromosomal deletion of the STAT5 binding site in LOUCY cells reduced protein levels of STAT5 in some MEF2C-positve T-ALL cell lines, and the presence of inhibitory IL7-JAK-STAT5 signaling highlighted the repressive impact of this factor in MEF2C regulation. Taken together, our results indicate that the expression of MEF2C in T-ALL cells is principally deregulated via activating leukemic transcription factors GFI1B or NKX2-5 and by escaping inhibitory developmental STAT5 signaling.
- Subjects :
- Chromatin Immunoprecipitation
Cancer Research
Transcription, Genetic
T cell
Blotting, Western
MADS Domain Proteins
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Proto-Oncogene Proteins c-myc
LYL1
Transcription (biology)
Proto-Oncogene Proteins
hemic and lymphatic diseases
Basic Helix-Loop-Helix Transcription Factors
STAT5 Transcription Factor
Tumor Cells, Cultured
medicine
Humans
MEF2C
RNA, Messenger
RNA, Small Interfering
Promoter Regions, Genetic
Transcription factor
STAT5
Homeodomain Proteins
Regulation of gene expression
biology
MEF2 Transcription Factors
Reverse Transcriptase Polymerase Chain Reaction
Hematology
Molecular biology
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
Repressor Proteins
Homeobox A10 Proteins
medicine.anatomical_structure
Myogenic Regulatory Factors
Oncology
Homeobox Protein Nkx-2.5
biology.protein
Chromatin immunoprecipitation
Transcription Factors
Subjects
Details
- ISSN :
- 10292403 and 10428194
- Volume :
- 52
- Database :
- OpenAIRE
- Journal :
- Leukemia & Lymphoma
- Accession number :
- edsair.doi.dedup.....870b5e8ae4b77c7cc87b86c9bd4a7cf2