Disorder-based T cell developmental order

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Scientists have discovered that an intrinsically disordered region in the transcription factor TCF-1 plays a vital role in coordinating T cell lineage commitment. This finding sheds light on the importance of these flexible protein domains in cellular function.

Many transcription factors contain intrinsically disordered regions whose functions are not well characterized. An intrinsically disordered region in TCF-1 has now been found to have an essential function in coordinating T cell lineage commitment.

A large fraction of eukaryotic proteomes, especially transcription factors1, contain intrinsically disordered regions (IDRs), which are polypeptide segments lacking well-defined structures. Because of their high flexibility, it is usually not feasible to study IDRs using X-ray crystallography, which has hindered the understanding of their biological relevance. Evidence suggests, however, that IDRs are not merely flexible linkers but rather protein domains with essential functions1. In this issue of Nature Immunology, Goldman et al.2 examine the function of IDRs in the transcription factor TCF-1 (T cell fate 1) during early T cell development. They find that the disordered region L1 serves an essential role in early T cell lineage commitment by repressing the expression of genes that lead to other lineages.

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