Regulation of the cleavage and polyadenylation machinery in 3′ end processing. (A) Some cleavage and polyadenylation (C/P) factors (yellow boxes) are recruited at the promoter by transcription activators (TAs) or other unknown mechanisms. (B) The pA is surrounded by several core cis elements, as indicated. The components of the C/P complex are indicated, and those binding to core elements are shown in red. Cleavage factor (CF)I and cleavage stimulation factor (CstF) are dimers, shown as two overlapping boxes. Phosphorylation of the RNA polymerase (RNAP) II carboxy terminal domain (CTD) is indicated. Splicing factors, such as U1 small nuclear ribonucleoprotein (snRNP), U2 snRNP, and U2AF65, interact with the C/P complex. Arrow indicates positive regulation of C/P and T-ended line indicates negative regulation. Two nucleosomes are shown (right), as well as attached symbols representing histone marks, such as H3K36me3. Other RNA-binding proteins (RBPs) can bind to sequences near the pA, thereby enhancing or inhibiting C/P. CPSF, cleavage and polyadenylation specificity factor; hFip1, human Fip1; PABPN, nuclear poly(A)-binding protein; PAP, poly(A) polymerase; PAS, polyadenylation signal; Wdr33, WD repeat domain 33.