Ctcf, also known as CCCTC-binding factor, is a ubiquitously expressed architectural protein that plays crucial roles in chromatin organization and gene regulation. It is involved in various biological processes such as transcriptional inhibition/activation, insulation, gene imprinting, and regulation of 3D chromatin structure [2]. Ctcf-mediated chromatin loops are important for enhancer-promoter interactions and cell fate specification [4,5]. Additionally, Ctcf has been linked to alternative splicing, further contributing to transcriptomic complexity [3].

In myogenic differentiation, the cooperation between Ctcf and lineage-specific pioneer transcription factors was validated using MyoD-null mice, Ctcf knockout mice, and CRISPR editing. Pioneer TFs facilitate Ctcf occupancy at lineage-specific sites, and together they form regulatory hubs to govern cell identity gene expression [4]. During pancreatic cell differentiation, Ctcf loops are formed and disassembled at different stages. New Ctcf loops lead to strengthened enhancer-promoter interactions and increased transcription of adjacent genes [5].

In conclusion, Ctcf is a key regulator in multiple biological processes, including cell fate specification and differentiation. The use of gene knockout mouse models in functional studies has provided insights into how Ctcf functions in these processes. Understanding Ctcf's role may contribute to a better understanding of diseases, such as cancer, where its genetic alterations have been identified [1].

References:

1. Debaugny, Roxanne E, Skok, Jane A. 2020. CTCF and CTCFL in cancer. In Current opinion in genetics & development, 61, 44-52. doi:10.1016/j.gde.2020.02.021. https://pubmed.ncbi.nlm.nih.gov/32334335/

2. Liu, Fangming, Wu, Duojiao, Wang, Xiangdong. 2018. Roles of CTCF in conformation and functions of chromosome. In Seminars in cell & developmental biology, 90, 168-173. doi:10.1016/j.semcdb.2018.07.021. https://pubmed.ncbi.nlm.nih.gov/30031212/

3. Alharbi, Adel B, Schmitz, Ulf, Bailey, Charles G, Rasko, John E J. . CTCF as a regulator of alternative splicing: new tricks for an old player. In Nucleic acids research, 49, 7825-7838. doi:10.1093/nar/gkab520. https://pubmed.ncbi.nlm.nih.gov/34181707/

4. Liu, Yuting, Wan, Xin, Li, Hu, Li, Cheng, Zhang, Yong. 2023. CTCF coordinates cell fate specification via orchestrating regulatory hubs with pioneer transcription factors. In Cell reports, 42, 113259. doi:10.1016/j.celrep.2023.113259. https://pubmed.ncbi.nlm.nih.gov/37851578/

5. Lyu, Xiaowen, Rowley, M Jordan, Kulik, Michael J, Dalton, Stephen, Corces, Victor G. 2023. Regulation of CTCF loop formation during pancreatic cell differentiation. In Nature communications, 14, 6314. doi:10.1038/s41467-023-41964-6. https://pubmed.ncbi.nlm.nih.gov/37813869/