Cell Cycle Regulation By the AML1B Transcription Factor

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DESCRIPTION (provided by applicant) The AML-1B gene product has been implicated in numerous translocations leading to leukemia. AML-1B is a transcription factor shown to be involved in hematopoietic differentiation. Our preliminary results show that over expressing wild-type AML-1B shortens the G1 phase of the cell cycle. The goals of this research are to identify the pathway(s) by which AML-1B affects cell cycle progression. We will use DNA microarray technology to ask what are the transcriptional targets of AML-1B, what pathways the targets feed into, and which targets are involved in the cell cycle phenotype observed for AML-1B. We will take advantage of the fact that AML-lB belongs to a family of transcription factors that all bind to the same enhancer motif. Yet out of this family, only AML-1B affects cell cycle progression. Therefore, by comparing transcriptional targets of AML-1B with one of its family members (AML-3) we should be able to eliminate numerous targets that are not likely to be involved in the cell cycle phenotype. This should increase the probability of successfully identifying targets of AML-1B which affect cell cycle progression. Thus leading the way for the identification of how the first transcription factor shown to shorten the G1 phase of the cell cycle accomplishes this feat.