# Multiple lineage-specific epigenetic landscapes at the antigen receptor loci

**Authors:** Xiang Qiu, Guanxiang Liang, Weiqiang Zhou, Ranjan Sen, Michael L. Atchison

PMC · DOI: 10.26599/agr.2023.9340010 · 2024-05-20

## TL;DR

This study compares epigenetic features of antigen receptor genes in different cell types, revealing distinct patterns in embryonic stem cells and immune cells.

## Contribution

The study identifies lineage-specific epigenetic landscapes at antigen receptor loci in ES cells and lymphocytes.

## Key findings

- AgR loci in ES cells show active histone modifications and transcription markers distinct from those in B and T cells.
- Active histone modifications in ES cells co-localize with binding sites for Oct4, Sox2, and Nanog.
- CTCF binding patterns overlap across ES cells, pro-B cells, and neurons despite other differences.

## Abstract

Antigen receptors (AgRs) expressed on B and T cells provide the adaptive immune system with ability to detect numerous foreign antigens. Epigenetic features of B cell receptor (BCR) and T cell receptor (TCR) genes were previously studied in lymphocytes, but little is known about their epigenetic features in other cells. Here, we explored histone modifications and transcription markers at the BCR and TCR loci in lymphocytes (pro-B, DP T cells, and mature CD4+ T cells), compared to embryonic stem (ES) cells and neurons. In B cells, the BCR loci exhibited active histone modifications and transcriptional markers indicative of active loci. Similar results were observed at the TCR loci in T cells. All loci were largely inactive in neurons. Surprisingly, in ES cells all AgR loci displayed a high degree of active histone modifications and markers of active transcription. Locations of these active histone modifications in ES cells were largely distinct from those in pro-B cells, and co-localized at numerous binding locations for transcription factors Oct4, Sox2, and Nanog. ES and pro-B cells also showed distinct binding patterns for the ubiquitous transcription factor YY1 and chromatin remodeler Brg1. On the contrary, there were many overlapping CCCTC-binding factor (CTCF) binding patterns when comparing ES cells, pro-B cells, and neurons. Our study identifies epigenetic features in ES cells and lymphocytes that may be related to ES cell pluripotency and lymphocyte tissue-specific activation at the AgR loci.

## Linked entities

- **Genes:** BCR (BCR activator of RhoGEF and GTPase) [NCBI Gene 613], Tcr (Third chromosome alpha methyl dopa-resistant) [NCBI Gene 47207], POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460], SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657], NANOG (Nanog homeobox) [NCBI Gene 79923], YY1 (YY1 transcription factor) [NCBI Gene 7528], SMARCA4 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4) [NCBI Gene 6597], CTCF (CCCTC-binding factor) [NCBI Gene 10664]

## Full-text entities

- **Genes:** Il2ra (interleukin 2 receptor, alpha chain) [NCBI Gene 16184] {aka CD25, Il2r, Ly-43}, da (dark) [NCBI Gene 13130], Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Yy1 (YY1 transcription factor) [NCBI Gene 22632] {aka NF-E1, YY-1}, NANOG (Nanog homeobox) [NCBI Gene 79923], Tcra (T cell receptor alpha chain) [NCBI Gene 21473] {aka Tcralpha}, Spn (sialophorin) [NCBI Gene 20737] {aka A630014B01Rik, Cd43, Galgp, Ly-48, Ly48}, Igkv9-129 (immunoglobulin kappa variable 9-129) [NCBI Gene 692182], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Foxo1 (forkhead box O1) [NCBI Gene 56458] {aka Afxh, FKHR, Fkhr1, Foxo1a}, Ctcf (CCCTC-binding factor) [NCBI Gene 13018], POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, SMARCA4 (SWI/SNF related BAF chromatin remodeling complex subunit ATPase 4) [NCBI Gene 6597] {aka BAF190, BAF190A, BRG1, CSS4, MRD16, OTSC12}, Spi1 (Spi-1 proto-oncogene) [NCBI Gene 20375] {aka Dis-1, Dis1, PU.1, Sfpi-1, Sfpi1, Spi-1}, Ighm (immunoglobulin heavy constant mu) [NCBI Gene 16019] {aka Igh-6, Igh-M, Igh6, Igm, TC1460681, muH}, Tcf3 (transcription factor 3) [NCBI Gene 21423] {aka A1, ALF2, E12, E12/E47, E2A, E47}, Polr2f (polymerase (RNA) II (DNA directed) polypeptide F) [NCBI Gene 69833] {aka 1810060D16Rik, RPB6}, TRBV20OR9-2 (T cell receptor beta variable 20/OR9-2 (non-functional)) [NCBI Gene 6962] {aka CDR3, TCRBV20S2, TCRBV2O, TCRBV2S2O}, Tcf7 (transcription factor 7, T cell specific) [NCBI Gene 21414] {aka TCF-1, Tcf1}, Pou5f1 (POU domain, class 5, transcription factor 1) [NCBI Gene 18999] {aka NF-A3, Oct-3, Oct-3/4, Oct-4, Oct3, Oct3/4}, Igh (immunoglobulin heavy chain complex) [NCBI Gene 111507], Smarca4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4) [NCBI Gene 20586] {aka BAF190A, Brg1, HP1-BP72, SNF2beta, SW1/SNF, b2b508.1Clo}, Rpia (ribose 5-phosphate isomerase A) [NCBI Gene 19895] {aka RPI}, Tcrb (T cell receptor beta chain) [NCBI Gene 21577] {aka TCRbeta, Tib}, H2-Ab1 (histocompatibility 2, class II antigen A, beta 1) [NCBI Gene 14961] {aka Abeta, H-2Ab, H2-Ab, I-Abeta, IAb, Ia-2}, Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}, Ebf1 (early B cell factor 1) [NCBI Gene 13591] {aka Ebf, O/E-1, OE-1, Olf-1, Olf1}, YY1 (YY1 transcription factor) [NCBI Gene 7528] {aka DELTA, GADEVS, INO80S, NF-E1, UCRBP, YIN-YANG-1}, Dad1 (defender against cell death 1) [NCBI Gene 13135], CTCF (CCCTC-binding factor) [NCBI Gene 10664] {aka CFAP108, FAP108, MRD21}, Tcrd (T cell receptor delta chain) [NCBI Gene 110066] {aka Tcrdelta}, Rag2 (recombination activating gene 2) [NCBI Gene 19374] {aka Rag-2}, Cd19 (CD19 antigen) [NCBI Gene 12478], Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, Nanog (Nanog homeobox) [NCBI Gene 71950] {aka 2410002E02Rik, ENK, Stm1, ecat4}, Rag1 (recombination activating 1) [NCBI Gene 19373] {aka Rag-1}, Id3 (inhibitor of DNA binding 3) [NCBI Gene 15903] {aka Hlh462, Idb3, bHLHb25}, Ikzf1 (IKAROS family zinc finger 1) [NCBI Gene 22778] {aka 5832432G11Rik, Ikaros, LyF-1, Zfpn1a1, Znfn1a1, hlk-1}, Sox2 (SRY (sex determining region Y)-box 2) [NCBI Gene 20674] {aka Sox-2, lcc, ysb}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Calca (calcitonin/calcitonin-related polypeptide, alpha) [NCBI Gene 12310] {aka CA, CGRP-1, CGRP1, Calc, Calc1, Cgrp}, Pax5 (paired box 5) [NCBI Gene 18507] {aka BSAP, EBB-1, KLP, Pax-5}
- **Diseases:** ES (MESH:D018236), pro-B (MESH:D006509)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049]
- **Mutations:** Chr5:142,891,416-142,920,715
- **Cell lines:** pro — Cricetulus griseus (Chinese hamster), Spontaneously immortalized cell line (CVCL_7182), ES — Gallus gallus (Chicken), Somatic stem cell (CVCL_JE75), E14 — Mus musculus (Mouse), Embryonic stem cell (CVCL_C320), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11103674/full.md

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Source: https://tomesphere.com/paper/PMC11103674