CTCF plays a key role in organizing chromatin into TAD structures but it can also function as a transcription factor. CTCFL (CTCF-like), the paralog of CTCF, is normally transiently expressed in pre-meiotic male germ cells together with ubiquitously expressed CTCF. It plays a unique role in spermatogenesis by regulating expression of testis-specific genes. Genetic alterations in CTCF and its paralog CTCFL have both been found in numerous cancers, but it remains unknown to what extent CTCFL deregulates transcription on its own or by opposing CTCF. Here, we discuss some of the potential mechanisms by which these two proteins could alter gene regulation and contribute to oncogenic transcriptional programs.
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