7/8/2023 0 Comments Typeeto faqThe resulting aberrant factors are oncoproteins that yield altered transcriptional patterns leading to the development of leukemia ( 54, 61). In hematological malignancies, transcription factors are often disrupted by chromosomal translocations and fused to genes encoding other transcriptional regulators ( 42, 51, 52). These proteins coordinate the sequential expression of gene products which results in progressive stages of progenitor cell commitment and differentiation ( 14, 57, 59). Myeloid and hematopoietic cell development is a complex process regulated by an extensive network of transcription factors (reviewed in references 58 and 61). This identifies ETO as a cofactor for a sequence-specific transcription factor and indicates that, like other corepressors, it functions through the action of histone deactylase. Corepression by ETO was completely abrogated by histone deacetylase inhibitors. The second repression domain (RD2) of PLZF, not the POZ/BTB domain, is necessary to bind to ETO. The N-terminal portion of ETO forms complexes with PLZF, while the C-terminal region, which was shown to bind to N-CoR and SMRT, is required for the ability of ETO to augment transcriptional repression by PLZF. The PLZF and ETO proteins associate in vivo and in vitro, and ETO can potentiate transcriptional repression by PLZF. We found that ETO is one of the corepressors recruited by PLZF. ![]() ![]() PLZF also mediates transcriptional repression through the actions of corepressors and histone deacetylases. ![]() The promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding transcriptional factor fused to retinoic acid receptor α in acute promyelocytic leukemia associated with the (11 17)(q23 q21) translocation. The resulting AML-1–ETO fusion is an aberrant transcriptional regulator due to the ability of ETO, which does not bind DNA itself, to recruit the transcriptional corepressors N-CoR, SMRT, and Sin3A and histone deacetylases. The ETO protein was originally identified by its fusion to the AML-1 transcription factor in translocation (8 21) associated with the M2 form of acute myeloid leukemia (AML).
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