Jorgensen Molecular Pathways of Bcl 11 a and Bcl 11 b in T - Cell Commitment

The development of T-cells from multipotent progenitors is highly regulated by a complex network of transcription factors, including Bcl11a and Bcl11b. Cells which do not properly undergo the transition to become committed cells will continue to proliferate above normal levels and become malignant. In the stepwise progression of T-cell development, Bcl11a is expressed in early stages when the progenitors are still able to give rise to multiple blood cell lineages, and is inactivated during commitment, while Bcl11b is activated during commitment, and is highly expressed during the T-cell specific stages of development. We seek to understand how the transcriptional changes Bcl11a and Bcl11b make during transition cause the cell to relinquish all other potential to become a T-cell. Using cDNA from DN3 cell lines infected with retroviruses containing Bcl11a and Bcl11b, we are running RT-qPCR analysis of a series of over fifty target genes the Rothenberg lab has determined to be significant in T-cell development, to quantify and analyze the transcriptional effects of Bcl11a and Bcl11b during commitment. Our results reveal not a simple antagonistic relationship between the opposing factors, but a complex interplay of both cooperative and conflicting efforts in gene regulation, which draw a new genetic map of commitment.