YY1 encodes the yin and yang 1 protein, a well-known zinc-finger transcription factor, whose name reflects its dual function: it has both activating and repressing effects on the transcription of genes. YY1 is involved in the regulation of a large number of genes, some of which play crucial roles in normal development and in the pathogenesis of various tumors.

Researchers from Nijmegen have now identified changes in YY1 as the cause of a new neurodevelopmental syndrome presenting with cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various malformations. In 23 patients with overlapping phenotypic features, they discovered de novo mutations in YY1. Further molecular investigations, including immunoprecipitation of YY1-bound chromatin, showed that the identified mutations and deletions resulted in haploinsufficiency of the protein. The decrease in function led to a massive loss of genome-wide YY1 binding and to alterations in histone acetylation. In particular, a specific decrease in H3K27 acetylation at YY1-bound enhancers reported by the authors suggests a hitherto neglected role of YY1 in enhancer regulation.

The results of this study have been published in the American Journal of Human Genetics.