PMC:7417788 / 30411-32220 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7417788","sourcedb":"PMC","sourceid":"7417788","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7417788","text":"Next, we focused on the differentially expressed transcription factors (DETs) in immune cells in the AA group compared to the YA group. At the TF level, MCs were the most affected by aging based on the numbers of upregulated and downregulated DETs (Fig. 4D and 4E). To identify aging-associated TF events, we performed an integrated comparative analysis of these DETs and found that AP-1 family TFs, including FOSL2 and JUNB, were increased in all immune cells during aging (Fig. 4D and 4E). Upregulation of AP-1 family TFs, including FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND, was also observed in almost all cell subsets during aging (Fig. 4F and 4I). The AP-1 family regulates a wide range of cellular processes, including cell proliferation, death, survival, and differentiation. The effects of the activated AP-1 TFs, associated with the active inflammatory state, are primarily mediated through combinatorial regulation with the NFAT family, both of which are key regulators of TC activation and are enriched in TCs (Fig. 4D) (Shaulian and Karin, 2002). In addition, we visualized the chromosomal accessibility of FOSL2 loci and NFATC2 loci and found that the chromosomal accessibility of the FOSL2 and NFATC2 gene regions was also increased in aged TCs (Fig. 4J and 4K). CDKN2B, an aging hallmark gene, also showed an increase in accessibility with age (Fig. 4L). In parallel, we found 25 common decreased TFs, including nuclear respiratory factor 1 (NRF1) and ELK4, which are involved in antioxidant stress and negatively regulate cell differentiation and proliferation (Figs. 4E and S8E–I). Consistently, we found that chromatin accessibility also decreased at the loci of SIRT7 (Fig. 4M), which coordinates with NRF1 to maintain cellular energy metabolism and proliferation (Mohrin et al., 2015).","tracks":[{"project":"LitCovid-PMC-OGER-BB","denotations":[{"id":"T710","span":{"begin":39,"end":48},"obj":"GO:0010467"},{"id":"T711","span":{"begin":81,"end":87},"obj":"UBERON:0002405;CL:0000738"},{"id":"T712","span":{"begin":88,"end":93},"obj":"CL:0000738"},{"id":"T713","span":{"begin":183,"end":188},"obj":"GO:0007568"},{"id":"T714","span":{"begin":278,"end":283},"obj":"GO:0007568"},{"id":"T715","span":{"begin":383,"end":387},"obj":"PR:000009232"},{"id":"T716","span":{"begin":410,"end":415},"obj":"PR:000007600"},{"id":"T717","span":{"begin":448,"end":454},"obj":"UBERON:0002405;CL:0000738"},{"id":"T718","span":{"begin":455,"end":460},"obj":"CL:0000738"},{"id":"T719","span":{"begin":468,"end":473},"obj":"GO:0007568"},{"id":"T720","span":{"begin":508,"end":512},"obj":"PR:000009232"},{"id":"T721","span":{"begin":633,"end":638},"obj":"GO:0007568"},{"id":"T722","span":{"begin":661,"end":665},"obj":"PR:000009232"},{"id":"T723","span":{"begin":673,"end":682},"obj":"GO:0065007"},{"id":"T724","span":{"begin":699,"end":717},"obj":"GO:0009987"},{"id":"T725","span":{"begin":729,"end":747},"obj":"GO:0008283"},{"id":"T726","span":{"begin":749,"end":754},"obj":"GO:0016265"},{"id":"T727","span":{"begin":816,"end":820},"obj":"PR:000009232"},{"id":"T728","span":{"begin":918,"end":928},"obj":"GO:0065007"},{"id":"T729","span":{"begin":987,"end":989},"obj":"CL:0002488;GO:0042110"},{"id":"T730","span":{"begin":990,"end":1000},"obj":"GO:0042110"},{"id":"T731","span":{"begin":1021,"end":1024},"obj":"CL:0002488"},{"id":"T732","span":{"begin":1123,"end":1128},"obj":"PR:000007600"},{"id":"T733","span":{"begin":1138,"end":1144},"obj":"PR:000011164"},{"id":"T734","span":{"begin":1202,"end":1207},"obj":"PR:000007600"},{"id":"T735","span":{"begin":1212,"end":1218},"obj":"PR:000011164"},{"id":"T736","span":{"begin":1219,"end":1223},"obj":"SO:0000704"},{"id":"T737","span":{"begin":1281,"end":1287},"obj":"PR:000000093"},{"id":"T738","span":{"begin":1292,"end":1297},"obj":"GO:0007568"},{"id":"T739","span":{"begin":1307,"end":1311},"obj":"SO:0000704"},{"id":"T740","span":{"begin":1431,"end":1438},"obj":"GO:0005634;PR:000011422"},{"id":"T741","span":{"begin":1439,"end":1450},"obj":"PR:000011422;GO:0045333"},{"id":"T742","span":{"begin":1451,"end":1459},"obj":"PR:000011422"},{"id":"T743","span":{"begin":1461,"end":1465},"obj":"PR:000011169"},{"id":"T744","span":{"begin":1471,"end":1475},"obj":"PR:000007027"},{"id":"T745","span":{"begin":1542,"end":1562},"obj":"GO:0030154"},{"id":"T746","span":{"begin":1631,"end":1640},"obj":"GO:0000785"},{"id":"T747","span":{"begin":1685,"end":1690},"obj":"PR:000014893"},{"id":"T748","span":{"begin":1725,"end":1729},"obj":"PR:000011169"},{"id":"T749","span":{"begin":1742,"end":1750},"obj":"GO:0008283"}],"attributes":[{"subj":"T710","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T711","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T712","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T713","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T714","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T715","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T716","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T717","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T718","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T719","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T720","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T721","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T722","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T723","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T724","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T725","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T726","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T727","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T728","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T729","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T730","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T731","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T732","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T733","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T734","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T735","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T736","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T737","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T738","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T739","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T740","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T741","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T742","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T743","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T744","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T745","pred":"source","obj":"LitCovid-PMC-OGER-BB"},{"subj":"T746","pred":"source","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