ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia

Autor: Lucia Altucci, Sadia Saeed, Hendrik G. Stunnenberg, Femke Simmer, Joost H.A. Martens, Edo Vellenga, Amit Mandoli, Bart-Jan Wierenga, Abhishek Singh
Přispěvatelé: Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Martens, Jh, Mandoli, A, Simmer, F, Wierenga, Bj, Saeed, S, Singh, Aa, Altucci, Lucia, Vellenga, E, Stunnenberg, H. G.
Rok vydání: 2012
Předmět:
FUSION PROTEIN
Proto-Oncogene Protein c-fli-1
Oncogene Proteins
Fusion
genetic structures
Chromosomes
Human
Pair 21
ACUTE PROMYELOCYTIC LEUKEMIA
Antigens
CD34
Biochemistry
DEFINITIVE HEMATOPOIESIS
Translocation
Genetic
Epigenesis
Genetic
Histones
chemistry.chemical_compound
RUNX1 Translocation Partner 1 Protein
hemic and lymphatic diseases
AML1-ETO
GENOME-WIDE ANALYSIS
Transcriptional Regulator ERG
Regulation of gene expression
Myeloid Neoplasia
Gene Expression Regulation
Leukemic
leukemia
STEM/PROGENITOR CELLS
Acetylation
Hematology
Cell biology
Leukemia
Myeloid
Acute
Cell Transformation
Neoplastic
RUNX1
Core Binding Factor Alpha 2 Subunit
CBF-BETA
RNA Interference
Erg
epigenetic
Chromosomes
Human
Pair 8
Protein Binding
EXPRESSION
Immunology
Biology
Humans
HEMATOPOIETIC STEM-CELLS
Nucleotide Motifs
Transcription factor
TRANSCRIPTION FACTOR ERG
Molecular Biology
Binding Sites
Proto-Oncogene Proteins c-ets
fungi
Cell Biology
Hematopoietic Stem Cells
Molecular biology
GENE
eye diseases
chemistry
Trans-Activators
Histone deacetylase
sense organs
Zdroj: Blood 120 (19) (2012): 4038–4048. doi:10.1182/blood-2012-05-429050
info:cnr-pdr/source/autori:Martens JH, Mandoli A, Simmer F, Wierenga BJ, Saeed S, Singh AA, Altucci L, Vellenga E, Stunnenberg HG./titolo:ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia./doi:10.1182%2Fblood-2012-05-429050/rivista:Blood/anno:2012/pagina_da:4038/pagina_a:4048/intervallo_pagine:4038–4048/volume:120 (19)
Blood, 120, 19, pp. 4038-4048
Blood, 120, 4038-4048
Blood, 120(19), 4038-4048. AMER SOC HEMATOLOGY
ISSN: 0006-4971
DOI: 10.1182/blood-2012-05-429050
Popis: ERG and FLI1 are closely related members of the ETS family of transcription factors and have been identified as essential factors for the function and maintenance of normal hematopoietic stem cells. Here genome-wide analysis revealed that both ERG and FLI1 occupy similar genomic regions as AML1-ETO in t(8;21) AMLs and identified ERG/FLI1 as proteins that facilitate binding of oncofusion protein complexes. In addition, we demonstrate that ERG and FLI1 bind the RUNX1 promoter and that shRNA-mediated silencing of ERG leads to reduced expression of RUNX1 and AML1-ETO, consistent with a role of ERG in transcriptional activation of these proteins. Finally, we identify H3 acetylation as the epigenetic mark preferentially associated with ETS factor binding. This intimate connection between ERG/FLI1 binding and H3 acetylation implies that one of the molecular strategies of oncofusion proteins, such as AML1-ETO and PML-RAR-α, involves the targeting of histone deacetylase activities to ERG/FLI1 bound hematopoietic regulatory sites. Together, these results highlight the dual importance of ETS factors in t(8;21) leukemogenesis, both as transcriptional regulators of the oncofusion protein itself as well as proteins that facilitate AML1-ETO binding.
Databáze: OpenAIRE
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