Role of Acinus in regulating retinoic acid-responsive gene pre-mRNA splicing.

Acinus-S' is a corepressor for retinoic acid receptor (RAR)-dependent gene transcription and has been suggested to be involved in RNA processing. In this study, the role of Acinus isoforms in regulating pre-mRNA splicing was explored using in vivo splicing assays. Both Acinus-L and Acinus-S', with the activity of Acinus-L higher than that of Acinus-S', increase the splicing of a retinoic acid (RA)-responsive minigene containing a weak 5' splice site but not a RA-responsive minigene containing a strong 5' splice site.

The SAP motif and C-terminal RS- and RD/E-rich region influences the sub-nuclear localization of Acinus isoforms.

Acinus has been reported to function in apoptosis, RNA processing and regulation of gene transcription including RA-dependent transcription. There are three different isoforms of Acinus termed Acinus-L, Acinus-S', and Acinus-S. The isoforms of Acinus differ in their N-terminus while the C-terminus is consistent in all isoforms.

Role of COUP-TFI during retinoic acid-induced differentiation of P19 cells to endodermal cells.

Retinoic acid (RA) is a positive regulator of P19 cell differentiation. Silencing of pre-B cell leukemia transcription factors (PBXs) expression in P19 cells (AS cells) results in a failure of these cells to differentiate to endodermal cells upon RA treatment. Chicken Ovalbumin Upstream Promoter Transcription Factor I (COUP-TFI) is an orphan member of the steroid-thyroid hormone superfamily.

Thymine DNA glycosylase is essential for active DNA demethylation by linked deamination-base excision repair.

DNA methylation is a major epigenetic mechanism for gene silencing. Whereas methyltransferases mediate cytosine methylation, it is less clear how unmethylated regions in mammalian genomes are protected from de novo methylation and whether an active demethylating activity is involved. Here, we show that either knockout or catalytic inactivation of the DNA repair enzyme thymine DNA glycosylase (TDG) leads to embryonic lethality in mice.

Role of SF-1 and DAX-1 during differentiation of P19 cells by retinoic acid.

Retinoic acid (RA) is critical for embryonic development and cellular differentiation. Previous work in our laboratory has shown that blocking the RA-dependent increase in pre-β cell leukemia transcription factors (PBX) mRNA and protein levels in P19 cells prevents endodermal and neuronal differentiation. Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1) and steroidogenic factor (SF-1) were found by microarray analysis to be regulated by PBX in P19 cells.