Ctcf, also known as CCCTC-binding factor, is a ubiquitously expressed architectural protein. It plays a crucial role in organizing chromatin into TAD structures, and can function as a transcription factor. Ctcf is involved in various biological processes such as transcriptional inhibition/activation, insulation, gene imprinting, and regulation of 3D chromatin structure [1,2]. It contributes to the formation and regulation of genome multi-dimensions and is essential for different biological procedures [2]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Ctcf's functions.

In MyoD-null mice, CTCF knockout mice, and during myogenic differentiation with CRISPR editing, it was demonstrated that CTCF cooperates with lineage-specific pioneer transcription factors (TFs) to control cell identity at 1D and 3D levels. Pioneer TFs facilitate CTCF occupancy at lineage-specific sites, and together they form regulatory hubs to govern cell identity gene expression [3]. In the differentiation of human embryonic stem cells into pancreatic islet organoids, CTCF loops are formed and disassembled at different stages. New CTCF loops strengthen enhancer-promoter interactions and increase transcription of genes adjacent to loop anchors, suggesting an important role for CTCF in controlling gene expression during cell differentiation [4].

In conclusion, Ctcf is a key regulator in chromatin organization and gene expression. Model-based research, especially KO/CKO mouse models, has revealed its significance in processes like cell fate specification and cell differentiation. Understanding Ctcf's functions provides insights into normal biological processes and may have implications for diseases where its function is disrupted, such as in cancers where genetic alterations in Ctcf and its paralog CTCFL have been found [1].