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Open Access 10-08-2022 | Pituitary Adenoma | Original Article

Global changes in chromatin accessibility and transcription in growth hormone-secreting pituitary adenoma

Authors: Meng Wang, Chenxing Ji, Yichao Zhang, Zhiqiang Zhang, Yu Zhang, Huiping Guo, Nidan Qiao, Xiang Zhou, Xiaoyun Cao, Zhen Ye, Yifei Yu, Vladimir Melnikov, Wei Gong, Min He, Zhaoyun Zhang, Yao Zhao, Xuelong Wang, Gang Wei, Zhao Ye

Published in: Endocrine | Issue 2/2022

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.

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Title: Global changes in chromatin accessibility and transcription in growth hormone-secreting pituitary adenoma
Authors: Meng Wang
Chenxing Ji
Yichao Zhang
Zhiqiang Zhang
Yu Zhang
Huiping Guo
Nidan Qiao
Xiang Zhou
Xiaoyun Cao
Zhen Ye
Yifei Yu
Vladimir Melnikov
Wei Gong
Min He
Zhaoyun Zhang
Yao Zhao
Xuelong Wang
Gang Wei
Zhao Ye
Publication date: 10-08-2022
Publisher: Springer US
Keyword: Pituitary Adenoma
Published in: Endocrine / Issue 2/2022
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-022-03155-z

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