Lupus & antiphospholipid syndrome

3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

Our results highlight the 3D genome structure alterations associated with SLE development

Study context

Population
Patients with systemic lupus erythematosus (SLE) and age-matched and sex-matched healthy controls; CD4+ T cells
Participants
7 vs 5
Comparison
CD4+ T cells of patients with SLE vs age-matched and sex-matched healthy controls (HCs)
  • SLEn = 7
  • HCsn = 5reference
Outcome
3D genome structure in CD4+ T cells
Methodological detailsHi-C, RNA sequencing, age-matched and sex-matched controls, Integrative analyses: transcription factor motif enrichment, SPI1 knockdown, histone modifications (H3K27ac, H3K4me1, H3K4me3)
  • Hi-C
  • RNA sequencing
  • Age-matched and sex-matched controls
  • Integrative analyses: transcription factor motif enrichment, SPI1 knockdown, histone modifications (H3K27ac, H3K4me1, H3K4me3)

Main finding

As reported in the abstract

  • 3D chromosome organisation in SLE T cells clearly distinct from HCs and closely associated with SLE disease activity
  • Loops within chromosomes associated with SLE disease activity and differentially expressed genes; key histone modifications close to these loops
  • Transcription factor SPI1, whose motif is in the altered loop in SLE, contributes to overexpression of interferon pathway gene
  • Potential influences of genetic variations in 3D genome alterations in SLE

Original publication

3D genome alterations in T cells associated with disease activity of systemic lupus erythematosus. Ann Rheum Dis. Published 1 September 2022. doi:10.1136/ard-2022-222653

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