Abstract
Ctip2/Bcl11b is a zinc finger transcription factor with dual action (repression/activation) that couples epigenetic regulation to gene transcription during the development of various tissues. It is involved in a variety of physiological responses under healthy and pathological conditions. Its role and mechanisms of action are best characterized in the immune and nervous systems. Furthermore, its implication in the development and homeostasis of other various tissues has also been reported. In the present review, we describe its role in skin development, adipogenesis, tooth formation and cranial suture ossification. Experimental data from several studies demonstrate the involvement of Bcl11b in the control of the balance between cell proliferation and differentiation during organ formation and repair, and more specifically in the context of stem cell self-renewal and fate determination. The impact of mutations in the coding sequences of Bcl11b on the development of diseases such as craniosynostosis is also presented. Finally, we discuss genome-wide association studies that suggest a potential influence of single nucleotide polymorphisms found in the 3’ regulatory region of Bcl11b on the homeostasis of the cardiovascular system.
Highlights
Since the discovery of the first mammalian transcription factor Sp1 and its corresponding DNA binding sequence (GC boxes) five decades ago (Dynan and Tjian, 1983), many other transcription factors with remarkable and complex features have been identified and have led to our current understanding of gene regulation/expression
The multisystem impact of Bcl11b mutations and single nucleotide polymorphisms (SNPs) in humans as well as the observed phenotypes in animal models suggests that Bcl11b, through its multiple partners, DNA interaction domains and diversity of target genes, regulates key processes in multiple tissues during embryonic development as well as in adulthood
Bcl11b seems to control the balance between cell proliferation and differentiation during organ formation and repair and, in the context of stem cell self-renewal and fate determination
Summary
Since the discovery of the first mammalian transcription factor Sp1 (a zinc finger protein) and its corresponding DNA binding sequence (GC boxes) five decades ago (Dynan and Tjian, 1983), many other transcription factors with remarkable and complex features have been identified and have led to our current understanding of gene regulation/expression. These studies and many others led to the notion that transcription factors play a crucial role in coupling actors of epigenetic regulation to gene expression and cell fate determination and tissue homeostasis.
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