Meng Wang1, Chenxing Ji2, Yichao Zhang2, Zhiqiang Zhang3, Yu Zhang3, Huiping Guo4, Nidan Qiao2,5, Xiang Zhou2,5, Xiaoyun Cao2,5, Zhen Ye2, Yifei Yu1, Vladimir Melnikov1, Wei Gong1, Min He1, Zhaoyun Zhang1, Yao Zhao2,5,6,7,8,9,10, Xuelong Wang11, Gang Wei12, Zhao Ye13,14. 1. Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. 2. Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China. 3. CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. 4. School of Life Sciences and Technology, Tongji University, Shanghai, China. 5. Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China. 6. Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China. 7. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China. 8. Sate Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China. 9. National Center for Neurological Disorders, Shanghai, China. 10. Neurosurgical Institute of Fudan University, Fudan University, Shanghai, China. 11. CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. wangxuelong@picb.ac.cn. 12. CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China. weigang@picb.ac.cn. 13. Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China. yezhaozj663812@126.com. 14. Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China. yezhaozj663812@126.com.
Abstract
PURPOSE: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA. METHODS: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA. RESULTS: Totally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site. CONCLUSIONS: Our results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease.
PURPOSE: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA. METHODS: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA. RESULTS: Totally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site. CONCLUSIONS: Our results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease.
Authors: Kandice R Levental; Hongmei Yu; Laura Kass; Johnathon N Lakins; Mikala Egeblad; Janine T Erler; Sheri F T Fong; Katalin Csiszar; Amato Giaccia; Wolfgang Weninger; Mitsuo Yamauchi; David L Gasser; Valerie M Weaver Journal: Cell Date: 2009-11-25 Impact factor: 41.582
Authors: Alexander Swoboda; Robert Soukup; Oliver Eckel; Katharina Kinslechner; Bettina Wingelhofer; David Schörghofer; Christina Sternberg; Ha T T Pham; Maria Vallianou; Jaqueline Horvath; Dagmar Stoiber; Lukas Kenner; Lionel Larue; Valeria Poli; Friedrich Beermann; Takashi Yokota; Stefan Kubicek; Thomas Krausgruber; André F Rendeiro; Christoph Bock; Rainer Zenz; Boris Kovacic; Fritz Aberger; Markus Hengstschläger; Peter Petzelbauer; Mario Mikula; Richard Moriggl Journal: Oncogene Date: 2020-12-15 Impact factor: 9.867
Authors: Jessica Tome-Garcia; Parsa Erfani; German Nudelman; Alexander M Tsankov; Igor Katsyv; Rut Tejero; Martin Walsh; Roland H Friedel; Elena Zaslavsky; Nadejda M Tsankova Journal: Nat Commun Date: 2018-10-01 Impact factor: 14.919