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Related Experiment Videos

Histone modifications associated with somatic hypermutation.

Valerie H Odegard1, Sean T Kim, Shannon M Anderson

  • 1Section of Immunobiology, Yale University School of Medicine, Box 208011, New Haven, Connecticut 06520, USA.

Immunity
|July 26, 2005
PubMed
Summary
This summary is machine-generated.

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Histone H2B phosphorylation at Serine 14 (H2B(Ser14P)) is a novel marker for somatic hypermutation (SHM) and class switch recombination (CSR). This modification, unlike others, directly correlates with active SHM in immunoglobulin loci.

Area of Science:

  • Immunology
  • Molecular Biology
  • Epigenetics

Background:

  • V(D)J recombination and class switch recombination (CSR) involve specific histone modifications like acetylation and H2AX phosphorylation (gammaH2AX).
  • The chromatin modifications associated with somatic hypermutation (SHM) in vivo remain largely uncharacterized.

Purpose of the Study:

  • To investigate the in vivo chromatin modifications associated with somatic hypermutation (SHM) within immunoglobulin loci.
  • To determine if known recombination-associated histone modifications are also linked to SHM.
  • To identify novel histone modifications specific to SHM.

Main Methods:

  • Analysis of histone modifications, including acetylation, H3-lysine 4 methylation, and H2AX phosphorylation (gammaH2AX), at immunoglobulin loci undergoing SHM.

Related Experiment Videos

  • Assessment of histone H2B phosphorylation at Serine 14 (H2B(Ser14P)) in relation to SHM and CSR.
  • Investigation of the role of Activation-Induced Deaminase (AID) and histone kinase Mst1 in H2B phosphorylation.

    • Main Results:

    • Histone acetylation and H3-lysine 4 methylation do not correlate with active SHM or its spatial location within immunoglobulin loci.
    • No significant association was found between SHM and gammaH2AX.
    • Histone H2B phosphorylation at Serine 14 (H2B(Ser14P)) shows a strong correlation with both SHM and CSR.
    • H2B(Ser14P) in immunoglobulin regions requires AID and may involve Mst1.

    Conclusions:

    • Somatic hypermutation (SHM) and class switch recombination (CSR) elicit distinct DNA damage responses.
    • Histone H2B phosphorylation at Serine 14 (H2B(Ser14P)) represents a novel histone modification pattern associated with SHM, occurring independently of gammaH2AX.