DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity

Roy, Roshni; Ramamoorthy, Senthilkumar; Shapiro, Benjamin D.; Kaileh, Mary; Hernandez, Dena G.; Sarantopoulou, Dimitra; Arepalli, Sampath; Boller, Sören; Singh, Amit; Bektas, Arsun; Kim, Jae-Kwan; Moore, Ann Zenobia; Tanaka, Toshiko; McKelvey, Julia; Zukley, Linda; Nguyen, Cuong K.; Wallace, Tonya; Dunn, Christopher; Wersto, Robert P.; Wood, William H.; Piao, Yulan; Becker, Kevin G.; Coletta, Christopher; De, Supriyo; Sen, Jyoti Misra; Battle, Alexis; Weng, Nan‐ping; Grosschedl, Rudolf; Ferrucci, Luigi; Sen, Ranjan

doi:10.1016/j.immuni.2021.10.001

Cited by 37 publications

(34 citation statements)

References 54 publications

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“…Previous studies have demonstrated that DNA methylation underlies the specification of immune cell lineages. Both innate and adaptive immune lineages are specified by distinct epigenetic mechanisms via combinatorial and context-dependent use of crucial transcription factors [ 38 ]. Our data showed that DNA methylation might involve in the immune dysregulation in the tumor microenvironment of early-stage lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer

Huang

Zhou

et al. 2023

Clin Epigenet

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Background To explore the possible carcinogenesis and help better diagnose and treat patients with synchronous multiple primary lung cancers (sMPLC), we systematically investigated the genetic and DNA methylation profiles of early-stage sMPLC and single primary lung cancer (SPLC) and explored the immune profiles in the tumor microenvironment. Methods Hundred and ninety-one patients with 191 nodules in the SPLC group and 132 patients with 295 nodules in the sMPLC group were enrolled. All the samples were subjected to wide panel-genomic sequencing. Genome-wide DNA methylation was assessed using the Infinium Human Methylation 850 K BeadChip. RNA-seq and CIBERSORT analyses were performed to identify the immune characteristics in these two groups. Results Lesions from sMPLC patients had lower TMB levels than that from SPLC patients. sMPLC had a similar genetic mutational landscape with SPLC, despite some subgroup genetic discrepancies. Distinct DNA methylation patterns were identified between the two groups. The differentially methylated genes were related to immune response pathways. RNA-seq analyses revealed more immune-related DEGs in sMPLC. Accordingly, more immune-related biological processes and pathways were identified in sMPLC. Aberrant DNA methylation was associated with the abnormal expression of immune-related genes. CIBERSORT analysis revealed the infiltration of immune cells was different between the two groups. Conclusion Our study for the first time demonstrated genetic, epigenetic, and immune profile discrepancies between sMPLC and SPLC. Relative to the similar genetic mutational landscape, the DNA methylation patterns and related immune profiles were significantly different between sMPLC and SPLC, indicating their essential roles in the initiation and development of sMPLC.

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Section: Discussionmentioning

confidence: 99%

Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer

Huang

Zhou

et al. 2023

Clin Epigenet

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“…Previous studies comparing DNA methylation in B and T cells found, almost exclusively, lineage-specific differential methylation that mapped to sites associated with combinations of transcription factor binding [ 61 ]. However, these studies did not consider the memory status of cells.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of the DNA methylation landscape in CD4, CD8, and B memory lineages

et al. 2022

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Background There is considerable evidence that epigenetic mechanisms and DNA methylation are critical drivers of immune cell lineage differentiation and activation. However, there has been limited coordinated investigation of common epigenetic pathways among cell lineages. Further, it remains unclear if long-lived memory cell subtypes differentiate distinctly by cell lineages. Results We used the Illumina EPIC array to investigate the consistency of DNA methylation in B cell, CD4 T, and CD8 T naïve and memory cells states. In the process of naïve to memory activation across the three lineages, we identify considerable shared epigenetic regulation at the DNA level for immune memory generation. Further, in central to effector memory differentiation, our analyses revealed specific CpG dinucleotides and genes in CD4 T and CD8 T cells with DNA methylation changes. Finally, we identified unique DNA methylation patterns in terminally differentiated effector memory (TEMRA) CD8 T cells compared to other CD8 T memory cell subtypes. Conclusions Our data suggest that epigenetic alterations are widespread and essential in generating human lymphocyte memory. Unique profiles are involved in methylation changes that accompany memory genesis in the three subtypes of lymphocytes.

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“…Hypomethylation can be applied to describe the unmethylated state of most CpG sites in a specific sequence that usually is methylated or as a general phenomenon affecting the bulk of the genome; this is a decrease in the proportion of methylated versus unmethylated cytosines [ 39 , 40 ]. DNA hypomethylation has been described in multiple diseases [ 41 ], especially neoplastic diseases [ 42 ]. Regarding autoimmunity, it has already been shown that hypomethylation can play a role in the pathogenesis of SLE [ 43 , 44 ].…”

Section: Mechanism Of Autoimmunity Induced By Hervsmentioning

confidence: 99%

Human endogenous retroviruses (HERV) and non-HERV viruses incorporated into the human genome and their role in the development of autoimmune diseases

Posso-Osorio

Tobón

Cañas

2021

Journal of Translational Autoimmunity

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Genomic incorporation of viruses as human endogenous retroviruses (HERVs) are components of our genome that possibly originated by incorporating ancestral of exogenous viruses. Their roles in the evolution of the human genome, gene expression, and the pathogenesis of autoimmune diseases (ADs) and neoplastic phenomena are the subject of intense research. This review analyzes the evolutionary and virological aspects of HERVs and other viruses that incorporate their genome into the human genome and have known role in the genesis of ADs. These insights are helpful to understand further the possible role in autoimmunity genesis of HERVs, other ancestral viruses no HERVs and modern viruses with the ability to incorporate into the human genome or interact with HERVs.

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DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity

Cited by 37 publications

References 54 publications

Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer

Genetic, DNA methylation, and immune profile discrepancies between early-stage single primary lung cancer and synchronous multiple primary lung cancer

Comparative analysis of the DNA methylation landscape in CD4, CD8, and B memory lineages

Human endogenous retroviruses (HERV) and non-HERV viruses incorporated into the human genome and their role in the development of autoimmune diseases

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