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The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression.

Jad N Kanbar, Shengyun Ma, Eleanor S Kim, Nadia S Kurd, Matthew S Tsai, Tiffani Tysl, Christella E Widjaja, Abigail E Limary, Brian Yee, Zhaoren He, Yajing Hao, Xiang-Dong Fu, Gene W Yeo, Wendy J Huang, John T Chang

The Journal of experimental medicine · 2022 · Vol. 219 (6)

PubMed ↗ DOI ↗ PMC full text ↗

Abstract

During an immune response to microbial infection, CD8+ T cells give rise to short-lived effector cells and memory cells that provide sustained protection. Although the transcriptional programs regulating CD8+ T cell differentiation have been extensively characterized, the role of long noncoding RNAs (lncRNAs) in this process remains poorly understood. Using a functional genetic knockdown screen, we identified the lncRNA Malat1 as a regulator of terminal effector cells and the terminal effector memory (t-TEM) circulating memory subset. Evaluation of chromatin-enriched lncRNAs revealed that Malat1 grouped with trans lncRNAs that exhibit increased RNA interactions at gene promoters and gene bodies. Moreover, we observed that Malat1 was associated with increased H3K27me3 deposition at a number of memory cell-associated genes through a direct interaction with Ezh2, thereby promoting terminal effector and t-TEM cell differentiation. Our findings suggest an important functional role of Malat1 in regulating CD8+ T cell differentiation and broaden the knowledge base of lncRNAs in CD8+ T cell biology.

Linked datasets 5

GSE203092 GSE · via ncbi_elink
GEO ↗

The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression

Mus musculus

GSE203086 GSE · via ncbi_elink
GEO ↗

The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression (scRNA-Seq)

Mus musculus

33 data files
FileTypeSize
Day_7_Control_1_S17_L008_R1_001.fastq.gz RNA-Seq 495.0 MB
Day_7_Control_1_S18_L008_R1_001.fastq.gz RNA-Seq 532.6 MB
Day_7_Control_1_S19_L008_R1_001.fastq.gz RNA-Seq 778.9 MB
Day_7_Control_1_S20_L008_R1_001.fastq.gz RNA-Seq 445.9 MB
Day_7_Control_2_S25_L008_R1_001.fastq.gz RNA-Seq 672.6 MB
Day_7_Control_2_S26_L008_R1_001.fastq.gz RNA-Seq 424.8 MB
Day_7_Control_2_S27_L008_R1_001.fastq.gz RNA-Seq 613.2 MB
Day_7_Control_2_S28_L008_R1_001.fastq.gz RNA-Seq 525.5 MB
Day_7_MALAT1_1_S21_L008_R1_001.fastq.gz RNA-Seq 539.2 MB
Day_7_MALAT1_1_S22_L008_R1_001.fastq.gz RNA-Seq 727.0 MB
Day_7_MALAT1_1_S23_L008_R1_001.fastq.gz RNA-Seq 505.4 MB
Day_7_MALAT1_1_S24_L008_R1_001.fastq.gz RNA-Seq 484.0 MB
Day_7_MALAT1_2_S29_L008_R1_001.fastq.gz RNA-Seq 612.0 MB
Day_7_MALAT1_2_S30_L008_R1_001.fastq.gz RNA-Seq 445.0 MB
Day_7_MALAT1_2_S31_L008_R1_001.fastq.gz RNA-Seq 793.5 MB
Day_7_MALAT1_2_S32_L008_R1_001.fastq.gz RNA-Seq 644.1 MB
SRR19217837_GSM6153601 RNA-Seq 672.0 MB
SRR19217838_GSM6153601 RNA-Seq 424.0 MB
SRR19217839_GSM6153601 RNA-Seq 613.0 MB
SRR19217840_GSM6153601 RNA-Seq 525.0 MB
SRR19217841_GSM6153600 RNA-Seq 495.0 MB
SRR19217842_GSM6153600 RNA-Seq 532.0 MB
SRR19217843_GSM6153600 RNA-Seq 778.0 MB
SRR19217844_GSM6153600 RNA-Seq 445.0 MB
SRR19217845_GSM6153599 RNA-Seq 612.0 MB
SRR19217846_GSM6153599 RNA-Seq 445.0 MB
SRR19217847_GSM6153599 RNA-Seq 793.0 MB
SRR19217848_GSM6153599 RNA-Seq 644.0 MB
SRR19217848.lite RNA-Seq 644.1 MB
SRR19217849_GSM6153598 RNA-Seq 539.0 MB
SRR19217850_GSM6153598 RNA-Seq 726.0 MB
SRR19217851_GSM6153598 RNA-Seq 505.0 MB
SRR19217852_GSM6153598 RNA-Seq 483.0 MB
GSE203091 GSE · via ncbi_elink
GEO ↗

The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression (CUT&RUN)

Mus musculus

25 data files
FileTypeSize
Malat1_MP_1.R1.fastq OTHER 1.8 GB
Malat1_MP_2.R1.fastq OTHER 2.0 GB
Malat1_TE_1.R1.fastq OTHER 1.9 GB
Malat1_TE_2.R1.fastq OTHER 2.1 GB
Malat1_TE_iso.R1.fastq OTHER 419.5 MB
NT_Malat1_iso.R1.fastq OTHER 430.3 MB
NT_MP_1.R1.fastq OTHER 1.2 GB
NT_MP_2.R1.fastq OTHER 1.4 GB
NT_MP_iso.R1.fastq OTHER 706.5 MB
NT_TE_1.R1.fastq OTHER 1.7 GB
NT_TE_2.R1.fastq OTHER 1.6 GB
NT_TE_iso.R1.fastq OTHER 471.4 MB
SRR19221346_GSM6153714 OTHER 706.0 MB
SRR19221347_GSM6153713 OTHER 430.0 MB
SRR19221348_GSM6153712 OTHER 471.0 MB
SRR19221349_GSM6153711 OTHER 419.0 MB
SRR19221350_GSM6153710 OTHER 1.4 GB
SRR19221351_GSM6153709 OTHER 1.2 GB
SRR19221352_GSM6153708 OTHER 2.0 GB
SRR19221352.lite OTHER 2.0 GB
SRR19221353_GSM6153707 OTHER 1.8 GB
SRR19221354_GSM6153706 OTHER 1.6 GB
SRR19221355_GSM6153705 OTHER 1.7 GB
SRR19221356_GSM6153704 OTHER 2.1 GB
SRR19221357_GSM6153703 OTHER 1.9 GB
GSE203089 GSE · via ncbi_elink
GEO ↗

The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression (GRID-Seq)

Mus musculus

24 data files
FileTypeSize
CD8_Day4_1_S5_L001_R1_001.fastq.gz OTHER 5.1 GB
CD8_Day4_1_S5_L002_R1_001.fastq.gz OTHER 5.3 GB
CD8_Day4_1_S5_L005_R1_001.fastq.gz OTHER 2.0 GB
CD8_Day4_1_S5_L006_R1_001.fastq.gz OTHER 2.0 GB
CD8_Day4_1_S5_L007_R1_001.fastq.gz OTHER 2.0 GB
CD8_Day4_1_S5_L008_R1_001.fastq.gz OTHER 2.0 GB
CD8_Day4_2_S6_L001_R1_001.fastq.gz OTHER 3.4 GB
CD8_Day4_2_S6_L002_R1_001.fastq.gz OTHER 3.5 GB
CD8_Day4_2_S6_L005_R1_001.fastq.gz OTHER 2.8 GB
CD8_Day4_2_S6_L006_R1_001.fastq.gz OTHER 2.8 GB
CD8_Day4_2_S6_L007_R1_001.fastq.gz OTHER 2.8 GB
CD8_Day4_2_S6_L008_R1_001.fastq.gz OTHER 2.8 GB
SRR19218122_GSM6153692 OTHER 2.8 GB
SRR19218123_GSM6153692 OTHER 2.8 GB
SRR19218124_GSM6153692 OTHER 2.8 GB
SRR19218125_GSM6153692 OTHER 2.8 GB
SRR19218126_GSM6153692 OTHER 3.4 GB
SRR19218127_GSM6153692 OTHER 3.5 GB
SRR19218128_GSM6153691 OTHER 2.0 GB
SRR19218129_GSM6153691 OTHER 2.0 GB
SRR19218130_GSM6153691 OTHER 2.0 GB
SRR19218131_GSM6153691 OTHER 2.0 GB
SRR19218132_GSM6153691 OTHER 5.1 GB
SRR19218133_GSM6153691 OTHER 5.3 GB
GSE203090 GSE · via ncbi_elink
GEO ↗

The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression (ChIP-Seq)

Mus musculus

80 data files
FileTypeSize
MALAT1_A12_Input_S13_L007_R1_001.fastq.gz ChIP-Seq 610.0 MB
MALAT1_A12_Input_S13_L008_R1_001.fastq.gz ChIP-Seq 620.6 MB
MALAT1_A12_Input_S21_L005_R1_001.fastq.gz ChIP-Seq 271.8 MB
MALAT1_A12_Input_S21_L006_R1_001.fastq.gz ChIP-Seq 269.3 MB
MALAT1_A1_H3K27me3_S1_L005_R1_001.fastq.gz ChIP-Seq 247.1 MB
MALAT1_A1_H3K27me3_S1_L006_R1_001.fastq.gz ChIP-Seq 244.2 MB
MALAT1_A1_H3K27me3_S1_L007_R1_001.fastq.gz ChIP-Seq 1005.6 MB
MALAT1_A1_H3K27me3_S1_L008_R1_001.fastq.gz ChIP-Seq 1.0 GB
MALAT1_A1_H3K4me3_S11_L005_R1_001.fastq.gz ChIP-Seq 309.3 MB
MALAT1_A1_H3K4me3_S11_L006_R1_001.fastq.gz ChIP-Seq 306.0 MB
MALAT1_A1_H3K4me3_S7_L007_R1_001.fastq.gz ChIP-Seq 155.9 MB
MALAT1_A1_H3K4me3_S7_L008_R1_001.fastq.gz ChIP-Seq 157.9 MB
MALAT1_A2_H3K27me3_S2_L005_R1_001.fastq.gz ChIP-Seq 223.7 MB
MALAT1_A2_H3K27me3_S2_L006_R1_001.fastq.gz ChIP-Seq 222.1 MB
MALAT1_A2_H3K27me3_S2_L007_R1_001.fastq.gz ChIP-Seq 1.1 GB
MALAT1_A2_H3K27me3_S2_L008_R1_001.fastq.gz ChIP-Seq 1.1 GB
MALAT1_A2_H3K4me3_S13_L005_R1_001.fastq.gz ChIP-Seq 332.4 MB
MALAT1_A2_H3K4me3_S13_L006_R1_001.fastq.gz ChIP-Seq 327.8 MB
MALAT1_A2_H3K4me3_S9_L007_R1_001.fastq.gz ChIP-Seq 169.1 MB
MALAT1_A2_H3K4me3_S9_L008_R1_001.fastq.gz ChIP-Seq 172.4 MB
NT_12_Input_S14_L007_R1_001.fastq.gz ChIP-Seq 448.6 MB
NT_12_Input_S14_L008_R1_001.fastq.gz ChIP-Seq 455.2 MB
NT_12_Input_S22_L005_R1_001.fastq.gz ChIP-Seq 323.7 MB
NT_12_Input_S22_L006_R1_001.fastq.gz ChIP-Seq 324.1 MB
NT_1_H3K27me3_S4_L007_R1_001.fastq.gz ChIP-Seq 682.4 MB
NT_1_H3K27me3_S4_L008_R1_001.fastq.gz ChIP-Seq 693.8 MB
NT_1_H3K27me3_S6_L005_R1_001.fastq.gz ChIP-Seq 134.1 MB
NT_1_H3K27me3_S6_L006_R1_001.fastq.gz ChIP-Seq 133.5 MB
NT_1_H3K4me3_S10_L007_R1_001.fastq.gz ChIP-Seq 207.5 MB
NT_1_H3K4me3_S10_L008_R1_001.fastq.gz ChIP-Seq 209.9 MB
NT_1_H3K4me3_S16_L005_R1_001.fastq.gz ChIP-Seq 300.7 MB
NT_1_H3K4me3_S16_L006_R1_001.fastq.gz ChIP-Seq 299.2 MB
NT_2_H3K27me3_S5_L007_R1_001.fastq.gz ChIP-Seq 933.1 MB
NT_2_H3K27me3_S5_L008_R1_001.fastq.gz ChIP-Seq 956.1 MB
NT_2_H3K27me3_S7_L005_R1_001.fastq.gz ChIP-Seq 256.6 MB
NT_2_H3K27me3_S7_L006_R1_001.fastq.gz ChIP-Seq 254.6 MB
NT_2_H3K4me3_S12_L007_R1_001.fastq.gz ChIP-Seq 328.3 MB
NT_2_H3K4me3_S12_L008_R1_001.fastq.gz ChIP-Seq 330.6 MB
NT_2_H3K4me3_S18_L005_R1_001.fastq.gz ChIP-Seq 300.9 MB
NT_2_H3K4me3_S18_L006_R1_001.fastq.gz ChIP-Seq 300.4 MB
SRR19217989_GSM6153702 ChIP-Seq 324.0 MB
SRR19217990_GSM6153702 ChIP-Seq 323.0 MB
SRR19217991_GSM6153702 ChIP-Seq 455.0 MB
SRR19217992_GSM6153702 ChIP-Seq 448.0 MB
SRR19217993_GSM6153701 ChIP-Seq 269.0 MB
SRR19217994_GSM6153701 ChIP-Seq 271.0 MB
SRR19217995_GSM6153701 ChIP-Seq 620.0 MB
SRR19217996_GSM6153701 ChIP-Seq 609.0 MB
SRR19217997_GSM6153700 ChIP-Seq 300.0 MB
SRR19217998_GSM6153700 ChIP-Seq 300.0 MB
SRR19217999_GSM6153700 ChIP-Seq 330.0 MB
SRR19218000_GSM6153700 ChIP-Seq 328.0 MB
SRR19218001_GSM6153699 ChIP-Seq 299.0 MB
SRR19218002_GSM6153699 ChIP-Seq 300.0 MB
SRR19218003_GSM6153699 ChIP-Seq 209.0 MB
SRR19218004_GSM6153699 ChIP-Seq 207.0 MB
SRR19218005_GSM6153698 ChIP-Seq 172.0 MB
SRR19218006_GSM6153698 ChIP-Seq 169.0 MB
SRR19218007_GSM6153698 ChIP-Seq 327.0 MB
SRR19218008_GSM6153698 ChIP-Seq 332.0 MB
SRR19218009_GSM6153697 ChIP-Seq 157.0 MB
SRR19218010_GSM6153697 ChIP-Seq 155.0 MB
SRR19218011_GSM6153697 ChIP-Seq 305.0 MB
SRR19218012_GSM6153697 ChIP-Seq 309.0 MB
SRR19218013_GSM6153696 ChIP-Seq 933.0 MB
SRR19218014_GSM6153696 ChIP-Seq 956.0 MB
SRR19218015_GSM6153696 ChIP-Seq 256.0 MB
SRR19218016_GSM6153696 ChIP-Seq 254.0 MB
SRR19218017_GSM6153695 ChIP-Seq 682.0 MB
SRR19218018_GSM6153695 ChIP-Seq 693.0 MB
SRR19218019_GSM6153695 ChIP-Seq 134.0 MB
SRR19218020_GSM6153695 ChIP-Seq 133.0 MB
SRR19218021_GSM6153694 ChIP-Seq 223.0 MB
SRR19218022_GSM6153694 ChIP-Seq 222.0 MB
SRR19218023_GSM6153694 ChIP-Seq 1.1 GB
SRR19218024_GSM6153694 ChIP-Seq 1.1 GB
SRR19218025_GSM6153693 ChIP-Seq 247.0 MB
SRR19218026_GSM6153693 ChIP-Seq 244.0 MB
SRR19218027_GSM6153693 ChIP-Seq 1005.0 MB
SRR19218028_GSM6153693 ChIP-Seq 1.0 GB

Potentially related datasets 4

These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.

Accession Source Title
GSE157072 GSE · GEO GEO ↗ RNA-Seq of CD8+ T cell subsets during LCMV infection III
GSE95237 GSE · GEO GEO ↗ Genome-wide maps of chromatin state and chromatin accessibility in CD8 T cell subsets
GSE72408 GSE · GEO GEO ↗ The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation
GSE203092 GSE · GEO GEO ↗ The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression

Analysis pipelines 7

Pipeline Assay Steps Dataset
GSE157072 RNA-seq Data Processing geo_data_processing RNA-seq 3 GSE157072
GSE203086 scRNA-seq Data Processing geo_data_processing scRNA-seq 10 GSE203086
GSE203089 Data Processing geo_data_processing — 19 GSE203089
GSE203090 ChIP-seq Data Processing geo_data_processing ChIP-seq 3 GSE203090
GSE203091 ChIP-seq Data Processing geo_data_processing ChIP-seq 6 GSE203091
GSE203092 scRNA-seq Data Processing geo_data_processing scRNA-seq 10 GSE203092
GSE72408 Microarray Data Processing geo_data_processing Microarray 1 GSE72408
Funding 14 grants
Grant Funder
S10 OD026929 NIH HHS (United States)
R01 HG004659 NHGRI NIH HHS (United States)
P30 CA023100 NCI NIH HHS (United States)
P30 DK120515 NIDDK NIH HHS (United States)
R01 AI129973 NIAID NIH HHS (United States)
P01 AI132122 NIAID NIH HHS (United States)
P30 NS047101 NINDS NIH HHS (United States)
R01 AI123202 NIAID NIH HHS (United States)
R01 GM124494 NIGMS NIH HHS (United States)
I01 BX005106 BLRD VA (United States)
R56 DK098808 NIDDK NIH HHS (United States)
R01 DK098808 NIDDK NIH HHS (United States)
P30KC063491 NIH HHS (United States)
P30DK120515 San Diego Digestive Diseases Research Center