Diagenode

The reference epigenome and regulatory chromatin landscape of chronic lymphocytic leukemia


Beekman R. et al.

Chronic lymphocytic leukemia (CLL) is a frequent hematological neoplasm in which underlying epigenetic alterations are only partially understood. Here, we analyze the reference epigenome of seven primary CLLs and the regulatory chromatin landscape of 107 primary cases in the context of normal B cell differentiation. We identify that the CLL chromatin landscape is largely influenced by distinct dynamics during normal B cell maturation. Beyond this, we define extensive catalogues of regulatory elements de novo reprogrammed in CLL as a whole and in its major clinico-biological subtypes classified by IGHV somatic hypermutation levels. We uncover that IGHV-unmutated CLLs harbor more active and open chromatin than IGHV-mutated cases. Furthermore, we show that de novo active regions in CLL are enriched for NFAT, FOX and TCF/LEF transcription factor family binding sites. Although most genetic alterations are not associated with consistent epigenetic profiles, CLLs with MYD88 mutations and trisomy 12 show distinct chromatin configurations. Furthermore, we observe that non-coding mutations in IGHV-mutated CLLs are enriched in H3K27ac-associated regulatory elements outside accessible chromatin. Overall, this study provides an integrative portrait of the CLL epigenome, identifies extensive networks of altered regulatory elements and sheds light on the relationship between the genetic and epigenetic architecture of the disease.

Tags
Antibody

Share this article

Published
June, 2018

Source

Products used in this publication

  • cut and tag antibody icon
    C15410196
    H3K27ac Antibody
  • cut and tag antibody icon
    C15410194
    H3K4me1 Antibody
  • cut and tag antibody icon
    C15410003-50
    H3K4me3 Antibody
  • ChIP-seq Grade
    C15410192
    H3K36me3 Antibody
  • cut and tag antibody icon
    C15410193
    H3K9me3 Antibody
  • cut and tag antibody icon
    C15410195
    H3K27me3 Antibody

Events

  • Long-Read Sequencing Meeting 2024
    Uppsala, Sweden
    Oct 21-Oct 23, 2024
  • NextGen Omics 2024
    London, UK
    Oct 23-Oct 25, 2024
  • FEBS 2024
    Budapest, Hungary
    Oct 28-Oct 31, 2024
  • 5th Danube Conference on Epigenetics
    Budapest, Hungary
    Oct 28-Oct 31, 2024
 See all events

 


       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy