Figure 9.

Model of the combinatorial transcription factor network regulating CCND1 expression in ERα-positive BCC. (A) The recruitment pattern of the key transcription factors involved in E2 regulation of CCND1 expression is shown. Competent enh2 is recognized by FoxA1 that triggers chromatin remodeling, allowing recruitment of additional transcription factors including Sp1 that make enh2 sensitive to E2 induction (poised). Upon E2 stimulation, ERα is predominantly loaded at enh2 and mediates E2 transcriptional induction through communication with the upstream regulatory sites. NFIC is a repressor that enables E2 to balance its regulation of CCND1 transcription. The CCND1 transcribed sequence is represented as a dotted line, andnucleosomes are represented as ellipses. (B) Transcription factor network involved in estrogen modulation of CCND1 expression in human BCC. Arrows indicate transcriptional activations. NFIC that serves as a transcriptional repressor is displayed in red.