3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus

OBJECTIVES: Three-dimensional (3D) genome alterations can dysregulate gene expression by rewiring physical interactions within chromosomes in a tissue-specific or cell-specific manner and lead to diseases. We aimed to elucidate the 3D genome structure and its role in gene expression networks dysregu...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Ming, Feng, Delong, Hu, Longyuan, Liu, Lin, Wu, Jiali, Hu, Zhi, Long, Haojun, Kuang, Qiqi, Ouyang, Lianlian, Lu, Qianjin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887402/
https://www.ncbi.nlm.nih.gov/pubmed/36690410
http://dx.doi.org/10.1136/ard-2022-222653
_version_ 1784880335206481920
author Zhao, Ming
Feng, Delong
Hu, Longyuan
Liu, Lin
Wu, Jiali
Hu, Zhi
Long, Haojun
Kuang, Qiqi
Ouyang, Lianlian
Lu, Qianjin
author_facet Zhao, Ming
Feng, Delong
Hu, Longyuan
Liu, Lin
Wu, Jiali
Hu, Zhi
Long, Haojun
Kuang, Qiqi
Ouyang, Lianlian
Lu, Qianjin
author_sort Zhao, Ming
collection PubMed
description OBJECTIVES: Three-dimensional (3D) genome alterations can dysregulate gene expression by rewiring physical interactions within chromosomes in a tissue-specific or cell-specific manner and lead to diseases. We aimed to elucidate the 3D genome structure and its role in gene expression networks dysregulated in systemic lupus erythematosus (SLE). METHODS: We performed Hi-C experiments using CD4(+) T cells from 7 patients with SLE and 5 age-matched and sex-matched healthy controls (HCs) combined with RNA sequencing analysis. Further integrative analyses, including transcription factor motif enrichment, SPI1 knockdown and histone modifications (H3K27ac, H3K4me1, H3K4me3), were performed for altered loop-associated gene loci in SLE. RESULTS: We deciphered the 3D chromosome organisation in T cells of patients with SLE and found it was clearly distinct from that of HCs and closely associated with the disease activity of SLE. Importantly, we identified loops within chromosomes associated with the disease activity of SLE and differentially expressed genes and found some key histone modifications close to these loops. Moreover, we demonstrated the contribution of the transcription factor SPI1, whose motif is located in the altered loop in SLE, to the overexpression of interferon pathway gene. In addition, we identified the potential influences of genetic variations in 3D genome alterations in SLE. CONCLUSIONS: Our results highlight the 3D genome structure alterations associated with SLE development and provide a foundation for future interrogation of the relationships between chromosome structure and gene expression control in SLE.
format Online
Article
Text
id pubmed-9887402
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher BMJ Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-98874022023-02-01 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus Zhao, Ming Feng, Delong Hu, Longyuan Liu, Lin Wu, Jiali Hu, Zhi Long, Haojun Kuang, Qiqi Ouyang, Lianlian Lu, Qianjin Ann Rheum Dis Systemic Lupus Erythematosus OBJECTIVES: Three-dimensional (3D) genome alterations can dysregulate gene expression by rewiring physical interactions within chromosomes in a tissue-specific or cell-specific manner and lead to diseases. We aimed to elucidate the 3D genome structure and its role in gene expression networks dysregulated in systemic lupus erythematosus (SLE). METHODS: We performed Hi-C experiments using CD4(+) T cells from 7 patients with SLE and 5 age-matched and sex-matched healthy controls (HCs) combined with RNA sequencing analysis. Further integrative analyses, including transcription factor motif enrichment, SPI1 knockdown and histone modifications (H3K27ac, H3K4me1, H3K4me3), were performed for altered loop-associated gene loci in SLE. RESULTS: We deciphered the 3D chromosome organisation in T cells of patients with SLE and found it was clearly distinct from that of HCs and closely associated with the disease activity of SLE. Importantly, we identified loops within chromosomes associated with the disease activity of SLE and differentially expressed genes and found some key histone modifications close to these loops. Moreover, we demonstrated the contribution of the transcription factor SPI1, whose motif is located in the altered loop in SLE, to the overexpression of interferon pathway gene. In addition, we identified the potential influences of genetic variations in 3D genome alterations in SLE. CONCLUSIONS: Our results highlight the 3D genome structure alterations associated with SLE development and provide a foundation for future interrogation of the relationships between chromosome structure and gene expression control in SLE. BMJ Publishing Group 2023-02 2022-09-01 /pmc/articles/PMC9887402/ /pubmed/36690410 http://dx.doi.org/10.1136/ard-2022-222653 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Systemic Lupus Erythematosus
Zhao, Ming
Feng, Delong
Hu, Longyuan
Liu, Lin
Wu, Jiali
Hu, Zhi
Long, Haojun
Kuang, Qiqi
Ouyang, Lianlian
Lu, Qianjin
3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
title 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
title_full 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
title_fullStr 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
title_full_unstemmed 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
title_short 3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus
title_sort 3d genome alterations in t cells associated with disease activity of systemic lupus erythematosus
topic Systemic Lupus Erythematosus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9887402/
https://www.ncbi.nlm.nih.gov/pubmed/36690410
http://dx.doi.org/10.1136/ard-2022-222653
work_keys_str_mv AT zhaoming 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT fengdelong 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT hulongyuan 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT liulin 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT wujiali 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT huzhi 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT longhaojun 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT kuangqiqi 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT ouyanglianlian 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus
AT luqianjin 3dgenomealterationsintcellsassociatedwithdiseaseactivityofsystemiclupuserythematosus