Fig. 6.

Proposed models of ZNF638’s mode of action on alternative splicing. Sequestration model (A). ZNF638 may affect splicing decisions by altering the balance between available inhibitory and activating splicing factors competing for their binding to the pre-mRNA. Via sequestration of HNRNP proteins like HNRPA1, ZNF638 may prevent their binding to splice sites on the pre-mRNA, increasing the availability of activating splicing factors, such as SF2. Facilitator model (B). The loading of ZNF638 on the promoters of its target genes via C/EBP responsive elements may facilitate the recruitment of SR proteins to the CTD of the polymerase II and to the nearby nascent pre-mRNA. A, B: Purple exon is an alternatively spliced exon. Pol II, RNA polymerase II.