Evaluation of cyclin D3 as a transcriptional regulator in a neutrophil differentiation model.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B897
Abstract ID: 5494

Presenting Author:
Sarah E Powers , Professor of Biology at Lewis Univ.

Abstract:

Cyclin D3 is known to regulate cell cycle entry during the G₁ to S transition by associating with its binding partners CDK4/6 upon mitogenic stimulation. Cyclin D3 has also been implicated as a transcriptional regulator, but the indirect mechanism employed is not known. The HL60 cell line was used as a model to investigate cyclin D3’s role in altered gene transcription as DMSO-driven differentiation into neutrophils is induced. We have validated this system by evaluating changes in gene expression indicative of progression to the terminal neutrophil state. Interestingly, ectopic expression of cyclin D3 in undifferentiated HL60 (uHL60) cells causes changes in gene expression to mirror that seen in differentiated (dHL60) cells without the need to treat with DMSO. We have also assessed a cohort of target genes hypothesized to be sensitive to cyclin D3-impacted gene transcription as cells transition from uHL60 to dHL60. For those genes that are differentially expressed between uHL60 and dHL60, many are also sensitive to ectopic expression of cyclin D3. Forced expression of cyclin D3 mutants in uHL60 cells suggests that a C-terminal domain within cyclin D3 is responsible for this observed regulation of gene expression, as three mutations (L215M, Q244R, P278R) abrogate the wild-type cyclin D3-induced differentiation gene signature. Ongoing studies aim to elucidate transcription factor binding partners that interact in complex with cyclin D3 to cause differential gene expression.