Project description:We identified genes expressed in mouse liver that are regulated by Cux2, a highly female-specific liver transcription factor whose expression is regulated by sex-dependent plasma GH patterns. Using siRNA to knockdown Cux2 expression in female liver, we show that female specific genes are predominantly repressed by Cux2 knockdown. In contrast, similar numbers of male-biased genes are repressed as are induced by Cux2 knockdown. A scrambled, non-specific siRNA was used as a control. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175)
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
Project description:We identified genes expressed in mouse liver that are regulated by Cux2, a highly female-specific liver transcription factor whose expression is regulated by sex-dependent plasma GH patterns. Using adenovirus to overexpress Cux2 (Adeno-Cux2) in male liver, we show that Cux2 represses ~35% of male-biased genes and induces/de-represses ~35% of female-biased genes. Adeno-CMV was used as a control for adenoviral infection. (Published in: TL Conforto et al 2012, Mol Cell Biol. 2012, 32:4611-4627. PubMed PMID: 22966202; PMCID: PMC3486175)
