@article{wu_jiang_zou_sun_wu_cui_huntress_peng_li_2022, title={Coupling high-throughput mapping with proteomics analysis delineates cis-regulatory elements at high resolution}, volume={50}, ISSN={["1362-4962"]}, DOI={10.1093/nar/gkab890}, abstractNote={Abstract
               Growing evidence suggests that functional cis-regulatory elements (cis-REs) not only exist in epigenetically marked but also in unmarked sites of the human genome. While it is already difficult to identify cis-REs in the epigenetically marked sites, interrogating cis-REs residing within the unmarked sites is even more challenging. Here, we report adapting Reel-seq, an in vitro high-throughput (HTP) technique, to fine-map cis-REs at high resolution over a large region of the human genome in a systematic and continuous manner. Using Reel-seq, as a proof-of-principle, we identified 408 candidate cis-REs by mapping a 58 kb core region on the aging-related CDKN2A/B locus that harbors p16INK4a. By coupling Reel-seq with FREP-MS, a proteomics analysis technique, we characterized two cis-REs, one in an epigenetically marked site and the other in an epigenetically unmarked site. These elements are shown to regulate the p16INK4a expression over an ∼100 kb distance by recruiting the poly(A) binding protein PABPC1 and the transcription factor FOXC2. Downregulation of either PABPC1 or FOXC2 in human endothelial cells (ECs) can induce the p16INK4a-dependent cellular senescence. Thus, we confirmed the utility of Reel-seq and FREP-MS analyses for the systematic identification of cis-REs at high resolution over a large region of the human genome.}, number={1}, journal={NUCLEIC ACIDS RESEARCH}, author={Wu, Ting and Jiang, Danli and Zou, Meijuan and Sun, Wei and Wu, Di and Cui, Jing and Huntress, Ian and Peng, Xinxia and Li, Gang}, year={2022}, month={Jan} }
 @article{nagarajan_cho_gyorke_nagarajan_ezzell_brochu_huntress_harrell_peng_2021, title={Tumor Necrosis Factor Alpha-Induced Interleukin-1 Alpha Synthesis and Cell Death Is Increased in Mouse Epithelial Cells Infected With Chlamydia muridarum}, volume={224}, ISSN={["1537-6613"]}, DOI={10.1093/infdis/jiab168}, abstractNote={Abstract
               Chlamydia trachomatis-genital infection in women can be modeled in mice using Chlamydia muridarum. Using this model, it has been shown that the cytokines tumor necrosis factor (TNF)α and interleukin (IL)-1α lead to irreversible tissue damage in the oviducts. In this study, we investigated the contribution of TNFα on IL-1α synthesis in infected epithelial cells. We show that C muridarum infection enhanced TNFα-induced IL-1α expression and release in a mouse epithelial cell line. In addition to IL-1α, several TNFα-induced inflammatory genes were also highly induced, and infection enhanced TNF-induced cell death. In the mouse model of genital infection, oviducts from mice lacking the TNFα receptor displayed minimal staining for IL-1α compared with wild-type oviducts. Our results suggest TNFα and IL-1α enhance each other’s downstream effects resulting in a hyperinflammatory response to chlamydial infection. We propose that biologics targeting TNF-induced IL-1α synthesis could be used to mitigate tissue damage during chlamydial infection.}, journal={JOURNAL OF INFECTIOUS DISEASES}, author={Nagarajan, Uma M. and Cho, Crescentia and Gyorke, Clare E. and Nagarajan, Shanmugam and Ezzell, J. Ashley and Brochu, Hayden and Huntress, Ian and Harrell, Erin and Peng, Xinxia}, year={2021}, month={Aug}, pages={S47–S55} }