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Related Concept Videos

General Transcription Factors01:30

General Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Transcription Factors02:16

Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Combinatorial Gene Control02:33

Combinatorial Gene Control

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Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
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Related Experiment Video

Updated: Jun 11, 2025

Generation of Human Chimeric Antigen Receptor Regulatory T Cells
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Histone marks identify novel transcription factors that parse CAR-T subset-of-origin, clinical potential and

S Fiorenza1, Y Zheng2,3, J Purushe4

  • 1Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. salvatore.fiorenza@sydney.edu.au.

Nature Communications
|September 27, 2024
PubMed
Summary
This summary is machine-generated.

Histone mark analysis reveals CAR-T cell states missed by transcriptomics. KLF7 transcription factor activity correlates with CAR-T cell accumulation in lymphoma patients, improving therapeutic potential insights.

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Area of Science:

  • Immunotherapy
  • Epigenetics
  • Cancer Biology

Background:

  • Chimeric antigen receptor-modified T cell (CAR-T) immunotherapy is a breakthrough for blood cancers.
  • Understanding T cell quality and CAR-T efficacy is complex, with transcriptomics limitations in capturing transient gene expression.

Purpose of the Study:

  • To investigate if histone methylation marks can better define CAR-T cell functional states and therapeutic potential compared to transcriptomics.
  • To identify novel biomarkers for CAR-T cell efficacy.

Main Methods:

  • Analysis of transcriptionally repressive and permissive histone methylation marks in human T cell subsets and derived CAR-T cells.
  • Comparison of CAR-T products from healthy donors and patients.
  • Examination of CAR-T products from a clinical trial (NCT01865617) for associations with in vivo CAR-T accumulation.

Main Results:

  • Histone mark analyses effectively differentiated naïve, central memory, and effector memory CD8+ T cell subsets and their derived CAR-T cells.
  • Significant differences were observed in CAR-T manufactured from central memory cells of healthy donors versus patients.
  • A novel association was found between the transcription factor KLF7 activity and in vivo CAR-T accumulation in lymphoma patients.
  • Over-expression of KLF7 enhanced in vitro CAR-T proliferation and IL-2 production.

Conclusions:

  • Histone mark analysis offers a valuable dataset for identifying functionally relevant genes that transcriptomics may overlook.
  • KLF7 emerges as a potential biomarker and therapeutic target for improving CAR-T cell efficacy in cancer treatment.