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Transcription regulator protein BACH2 (BTB and CNC homolog 2)


Age-related changes in the BACH2 and PRDM1 genes in lymphocytes from healthy donors and chronic lymphocytic leukemia patients.

Age-related genetic changes in lymphocyte subsets are not currently well documented. BACH2 is a transcription factor that plays an important role in immune-mediated homeostasis by tightly regulating PRDM1 expression in both B-cells and T-cells. BACH2 gene expression is highly sensitive to DNA damage in aged mice. This concept led us to investigate the variation in BACH2 and also PRDM1 expression in major lymphocyte subsets with age. Lymphocyte subsets from 60 healthy donors, aged from 20 to 90 years, and 41 untreated chronic lymphocytic leukemia patients were studied. BACH2 and PRDM1 gene expression was analyzed by real-time quantitative PCR. BACH2 gene expression was correlated with its protein expression. Lymphocyte apoptosis was evaluated after intracellular oxidative stress-inducing etoposide treatment of T and B cells. Our analysis shows BACH2 mRNA downregulation with age in healthy donor CD4 , CD8 T-cells and CD19 B-cells. Decreased BACH2 expression was also correlated with an age-related reduction in CD8   CD28 T-cells. We found a strong correlation between age-related BACH2 downregulation and decreased CD4 T-cell and CD19 B-cell apoptosis. PRDM1, as expected, was significantly upregulated in CD4 T-cells, CD8 T-cells and CD19 B-cells, and inversely correlated with BACH2. A comparison of untreated chronic lymphocytic leukemia patients with age-matched healthy donors reveals that BACH2 mRNA expression was further reduced in CD4 T-cells, CD8 T-cells and leukemic-B cells. PRDM1 gene expression was consequently significantly upregulated in CD4 and CD8 T-cells in chronic lymphocytic leukemia patients but not in their leukemic B-cells. Overall, our data suggest that BACH2 and PRDM1 genes are significantly correlated with age in human immune cells and may be involved in immunosenescence.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Basic-Leucine Zipper Transcription Factors
  • Cellular Senescence
  • Down-Regulation
  • Female
  • Healthy Volunteers
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Lymphocyte Subsets
  • Male
  • Middle Aged
  • Positive Regulatory Domain I-Binding Factor 1
  • RNA, Messenger
  • Up-Regulation
  • Young Adult


  • Apoptosis
  • BACH2
  • Chronic lymphocytic leukemia
  • Immunosenescence
  • Lymphocytes
  • PRDM1

BACH2: a marker of DNA damage and ageing.

DNA damage and ageing share expression changes involving alterations in many aspects of metabolism, suppression of growth and upregulation of defence and genome maintenance systems. "Omics" technologies have permitted large-scale parallel measurements covering global cellular constituents and aided the identification of specific response pathways that change during ageing and after DNA damage. We have set out to identify genes with highly conserved response patterns through meta-analysis of mRNA expression datasets collected during natural ageing and accelerated ageing caused by a Transcription-Coupled Nucleotide Excision Repair (TC-NER) defect in a diverse set of organs and tissues in mice, and from in vitro UV-induced DNA damage in a variety of murine cells. The identified set of genes that show similar expression patterns in response to organ ageing (accelerated and normal), and endogenously and exogenously induced DNA damage, consists of genes involved in anti-oxidant systems and includes the transcription factor Bach2 as one of the most consistent markers. BACH2 was originally identified as a partner of the small Maf proteins and antagonist of the NRF2 anti-oxidant defence pathway and has been implicated in B-cell differentiation and immune system homeostasis. Although BACH2 has never before been associated with UV-induced damage or ageing, it shows a strong downregulation in both conditions. We have characterized the dynamics of Bach2 expression in response to DNA damage and show that it is a highly sensitive responder to transcription-blocking DNA lesions. Gene expression profiling using Affymetrix microarray analysis after siRNA-mediated silencing of Bach2 identified cell cycle and transcription regulation as the most significantly altered processes consistent with a function as transcription factor affecting proliferation.

MeSH Terms

  • Aging
  • Animals
  • Basic-Leucine Zipper Transcription Factors
  • Biomarkers
  • Cell Survival
  • DNA Damage
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Mice
  • Models, Animal
  • NIH 3T3 Cells
  • Oligonucleotide Array Sequence Analysis
  • Radiation, Ionizing
  • Ultraviolet Rays


  • Ageing
  • BACH2
  • DNA damage
  • Meta-analysis
  • NRF2