Haiqing Xu

All Publications

• A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis. The Journal of experimental medicine Ashkin, E. L., Tang, Y. J., Xu, H., Hung, K. L., Belk, J. A., Cai, H., Lopez, S. S., Dolcen, D. N., Hebert, J. D., Li, R., Ruiz, P. A., Keal, T., Andrejka, L., Chang, H. Y., Petrov, D. A., Dixon, J. R., Xu, Z., Winslow, M. M. 2025; 222 (1)

  Abstract

  The cohesin complex is a critical regulator of gene expression. STAG2 is the most frequently mutated cohesin subunit across several cancer types and is a key tumor suppressor in lung cancer. Here, we coupled somatic CRISPR-Cas9 genome editing and tumor barcoding with an autochthonous oncogenic KRAS-driven lung cancer model and showed that STAG2 is uniquely tumor-suppressive among all core and auxiliary cohesin components. The heterodimeric complex components PAXIP1 and PAGR1 have highly correlated effects with STAG2 in human lung cancer cell lines, are tumor suppressors in vivo, and are epistatic to STAG2 in oncogenic KRAS-driven lung tumorigenesis in vivo. STAG2 inactivation elicits changes in gene expression, chromatin accessibility, and 3D genome conformation that impact the cancer cell state. Gene expression and chromatin accessibility similarities between STAG2- and PAXIP1-deficient neoplastic cells further relate STAG2-cohesin to PAXIP1/PAGR1. These findings reveal a STAG2-PAXIP1/PAGR1 tumor-suppressive axis and uncover novel PAXIP1-dependent and PAXIP1-independent STAG2-cohesin-mediated mechanisms of lung tumor suppression.

  View details for DOI 10.1084/jem.20240765

  View details for PubMedID 39652422

• Chance promoter activities illuminate the origins of eukaryotic intergenic transcriptions. Nature communications Xu, H., Li, C., Xu, C., Zhang, J. 2023; 14 (1): 1826

  Abstract

  It is debated whether the pervasive intergenic transcription from eukaryotic genomes has functional significance or simply reflects the promiscuity of RNA polymerases. We approach this question by comparing chance promoter activities with the expression levels of intergenic regions in the model eukaryote Saccharomyces cerevisiae. We build a library of over 105 strains, each carrying a 120-nucleotide, chromosomally integrated, completely random sequence driving the potential transcription of a barcode. Quantifying the RNA concentration of each barcode in two environments reveals that 41-63% of random sequences have significant, albeit usually low, promoter activities. Therefore, even in eukaryotes, where the presence of chromatin is thought to repress transcription, chance transcription is prevalent. We find that only 1-5% of yeast intergenic transcriptions are unattributable to chance promoter activities or neighboring gene expressions, and these transcriptions exhibit higher-than-expected environment-specificity. These findings suggest that only a minute fraction of intergenic transcription is functional in yeast.

  View details for DOI 10.1038/s41467-023-37610-w

  View details for PubMedID 37005399