The first genome-wide mapping of endogenous UTY occupancy in human cells reveals that this Y-chromosome gene retains partial regulatory activity in early development—a potential snapshot of a gene in the process of evolutionary loss.
Y Chromosome Gene Retains Residual Function in Human Development, Study Finds
A study published in Development (Volume 153, Issue 9) on May 14, 2026, reports the first genome-wide mapping of endogenous UTY occupancy in human cells. The research demonstrates that UTY, a Y-chromosome gene, retains partial regulatory activity in early human development, despite its low expression and reduced enzymatic activity.
The human Y chromosome has lost most ancestral genes over evolutionary time, but UTY and a few others have persisted. The reasons for this retention have been unclear.
Mapping a Difficult Target
Using CRISPR-Cas9 genome editing in human embryonic stem cells, researchers tagged UTY and its X-chromosome homolog UTX with 3×FLAG-HA epitopes. Dual-crosslinking ChIP-seq allowed high-resolution detection of UTY genomic localization, which had been technically challenging due to UTY's low expression and poor antibody performance.
Key Findings
- UTY co-occupies active cis-regulatory elements with UTX and contributes to proper localization of pluripotency factors OCT4 and SOX2.
- UTY occupancy was weaker and less extensive than UTX occupancy.
- Combined disruption of UTY and UTX altered transcription factor localization and destabilized pluripotency without major global changes in H3K27me3, indicating non-catalytic chromatin regulatory cooperation.
The authors suggest UTY may represent a gene undergoing evolutionary loss while retaining residual biological function.
Expert Commentary
Dr. Tomohiko Akiyama (Yokohama City University) said:
"This may represent a snapshot of an evolutionary transition. UTY is still functional, but its expression and genomic occupancy are considerably lower than UTX. It is possible that we are observing a gene that is in the process of evolutionary loss, yet still retains residual biological function."