Xiangyu Shen
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Xiangyu Shen has a total of 5 co-authors. Here are the top co-authors by number of shared publications:
- Amanda E. Jones
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
1 shared publication - Chunxu Chen
Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
1 shared publication - Gengsheng Cao
School of life Sciences, Henan University, Kaifeng 475004, China
1 shared publication - Hengbin Wang
Department of Internal Medicine, Division of Hematology, Oncology and Palliative Care, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA
1 shared publication - Xiaokun Jian
Navy Medical Centre, Naval Medical University, Shanghai 200433, China
1 shared publication
Latest Publications
- Open Access
Divergent Mechanisms of H2AZ.1 and H2AZ.2 in PRC1-Mediated H2A Ubiquitination
The histone H2A variant H2AZ plays pivotal roles in shaping chromatin architecture and regulating gene expression. We recently identified H2AZ.2 in histone H2A lysine 119 ubiquitination (H2AK119ub)-enriched nucleosomes, but it is not known whether its highly related isoform H2AZ.1 also regulates this modification. In this study, we employed isoform-specific epitope-tagged knock-in mouse embryonic stem cell (ESC) lines to dissect the roles of each isoform in Polycomb Repressive Complex 1 (PRC1)-mediated H2AK119ub. Our results show that H2AZ.1 and H2AZ.2 share highly overlapping genomic binding profiles, both co-localizing extensively with H2AK119ub-enriched loci. The knockdown of either isoform led to reduced H2AK119ub levels; however, the two isoforms appear to function through distinct mechanisms. H2AZ.1 facilitates the recruitment of Ring1B, the catalytic subunit of PRC1, thereby promoting the deposition of H2AK119ub. In contrast, H2AZ.2 does not significantly affect Ring1B recruitment but instead functions as a structural component that stabilizes H2AK119ub-modified nucleosomes. In vitro ubiquitination assays indicate that H2AZ.1-containing nucleosomes serve as more efficient substrates for PRC1-mediated ubiquitination compared to those containing H2AZ.2. Thus, these findings define the distinct mechanisms of the two H2AZ variants in regulated PRC1-mediated H2AK119 ubiquitination and highlight a functional division of labor in epigenetic regulation.
Open AccessDivergent Mechanisms of H2AZ.1 and H2AZ.2 in PRC1-Mediated H2A Ubiquitination
The histone H2A variant H2AZ plays pivotal roles in shaping chromatin architecture and regulating gene expression. We recently identified H2AZ.2 in histone H2A lysine 119 ubiquitination (H2AK119ub)-enriched nucleosomes, but it is not known whether its highly related isoform H2AZ.1 also regulates this modification. In this study, we employed isoform-specific epitope-tagged knock-in mouse embryonic stem cell (ESC) lines to dissect the roles of each isoform in Polycomb Repressive Complex 1 (PRC1)-mediated H2AK119ub. Our results show that H2AZ.1 and H2AZ.2 share highly overlapping genomic binding profiles, both co-localizing extensively with H2AK119ub-enriched loci. The knockdown of either isoform led to reduced H2AK119ub levels; however, the two isoforms appear to function through distinct mechanisms. H2AZ.1 facilitates the recruitment of Ring1B, the catalytic subunit of PRC1, thereby promoting the deposition of H2AK119ub. In contrast, H2AZ.2 does not significantly affect Ring1B recruitment but instead functions as a structural component that stabilizes H2AK119ub-modified nucleosomes. In vitro ubiquitination assays indicate that H2AZ.1-containing nucleosomes serve as more efficient substrates for PRC1-mediated ubiquitination compared to those containing H2AZ.2. Thus, these findings define the distinct mechanisms of the two H2AZ variants in regulated PRC1-mediated H2AK119 ubiquitination and highlight a functional division of labor in epigenetic regulation.