Assay for Transposase-Accessible Chromatin Using Sequencing Analysis Reveals a Widespread Increase in Chromatin Accessibility in Psoriasis

Tang, Lili; Wang, Meng; Shen, Changbing; Wen, Leilei; Li, Mengqing; Wang, Dan; Zheng, Xiaodong; Yu, Shengquan; Wu, Wenjuan; Zhang, Chaowen; Zhang, Xuejun; Zhou, Fusheng

doi:10.1016/j.jid.2020.12.031

Cited by 10 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on our RNA-seq and ATAC-seq data, we used BETA-plus to integrate differentially expressed genes and open accessible peaks [ 9 , 15 ]. BETA identified 408 upregulated genes (rank product < 0.01, Additional file 6 : Table S1) and 133 downregulated genes (Ratio up/down = 3.1).…”

Section: Resultsmentioning

confidence: 99%

“…To further annotate 408 genes with accessibility peaks, we looked at whether these peaks can be interpreted by other epigenetic modifications. Based on our genome-wide DNA methylation dataset previously generated from the same samples, we extracted methylation levels for loci located within the accessible peaks [ 9 ]. For the 18 methylation loci located within 408 peaks, we found all accessible peaks marked by hypomethylation compared with normal controls (Additional file 7 : Table S2).…”

Section: Resultsmentioning

confidence: 99%

“…The ATAC-seq and transcriptome sequencing data were from two previous studies, and detailed information of enrolled samples has been described [ 9 , 15 ]. Briefly, patients were based on the following criteria: (i) at least one well-demarcated, erythematous, scaly lesion verified by two dermatologists; (ii) confirmation of each lesion-bearing tissue by clinical histopathology; (iii) no systemic anti-psoriatic treatment for 2 weeks before skin biopsy; and (iv) no topical anti-psoriatic treatment for 1 week before the biopsy.…”

Section: Methodsmentioning

confidence: 99%

“…It provides the whole open chromatin across the entire genome at one time, exploring transcription factor binding and gene expression regulation, which has been widely used in various diseases [ 8 ], including psoriasis. Utilizing ATAC-seq on 15 psoriatic lesions, 9 non-psoriatic lesions, and 19 normal healthy skin tissues, we previously identified 4,195 differentially accessible regions [ 9 ]. Further analysis showed that the sequence of differentially accessible regions was enriched in the FRA1/AP-1 transcription factor binding region [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Utilizing ATAC-seq on 15 psoriatic lesions, 9 non-psoriatic lesions, and 19 normal healthy skin tissues, we previously identified 4,195 differentially accessible regions [ 9 ]. Further analysis showed that the sequence of differentially accessible regions was enriched in the FRA1/AP-1 transcription factor binding region [ 9 ]. Upregulation of AP-1 family members has been shown in psoriatic skins, but the exact mechanism is not precise [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Chromatin accessibility and transcriptome integrative analysis revealed AP-1-mediated genes potentially modulate histopathology features in psoriasis

Tang

Zhang

et al. 2022

Clin Epigenet

Self Cite

View full text Add to dashboard Cite

Background Psoriasis is a chronic and hyperproliferative skin disease featured by hyperkeratosis with parakeratosis, Munro micro-abscess, elongation of rete pegs, granulosa thinning, and lymphocyte infiltration. We previously profiled gene expression and chromatin accessibility of psoriatic skins by transcriptome sequencing and ATAC-seq. However, integrating both of these datasets to unravel gene expression regulation is lacking. Here, we integrated transcriptome and ATAC-seq of the same psoriatic and normal skin tissues, trying to leverage the potential role of chromatin accessibility and their function in histopathology features. Results By inducing binding and expression target analysis (BETA) algorithms, we explored the target prediction of transcription factors binding in 15 psoriatic and 19 control skins. BETA identified 408 upregulated genes (rank product < 0.01) and 133 downregulated genes linked with chromatin accessibility. We noticed that cumulative fraction of genes in upregulation group was statistically higher than background, while that of genes in downregulation group was not significant. KEGG pathway analysis showed that the upregulated 408 genes were enriched in TNF, NOD, and IL-17 signaling pathways. In addition, the motif module in BETA suggested the 57 upregulated genes are targeted by transcription factor AP-1, indicating that increased chromatin accessibility facilitated the binding of AP-1 to the target regions and further induced expression of relevant genes. Among these genes, SQLE, STRN, EIF4, and MYO1B expression was increased in patients with hyperkeratosis, parakeratosis, and acanthosis thickening. Conclusions In summary, with the advantage of BETA, we identified a series of genes that contribute to the disease pathogenesis, especially in modulating histopathology features, providing us with new clues in treating psoriasis.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%