BCL6 promoter interacts with far upstream sequences with greatly enhanced activating histone modifications in germinal center B cells

Himabindu Ramachandrareddy, Alyssa Bouska, Yulei Shen, Ming Ji, A Angie Rizzino, Wing C. Chan, Timothy W. McKeithan

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

BCL6 encodes a transcriptional repressor that is essential for the germinal center (GC) reaction and important in lymphomagenesis. Although its promoter has been well studied, little is known concerning its possible regulation by more distal elements. To gain such information, we mapped critical histone modifications associated with active transcription within BCL6 as well as far upstream sequences at nucleosomal resolution in B-cell lines and in normal naive and GC B cells. Promoter-associated and intronic CpG islands (CGIs) in BCL6 showed a reciprocal pattern of histone modifications. Gene expression correlated with a paradoxical loss from the intronic CGI of histone H3 lysine-4 trimethylation, normally associated with transcription, suggesting that the intronic CGI may interfere with transcription. In an ∼110-kb region extending 150-260 kb upstream of BCL6, highly active histone modifications were present only in normal GC B cells and a GC B-cell line; this region overlaps with an alternative breakpoint region for chromosomal translocations and contains a GC-specific noncoding RNA gene. By chromosome conformation capture, we determined that the BCL6 promoter interacts with this distant upstream region. It is likely that transcriptional enhancers in this region activate BCL6 and overcome strong autorepression in GC B cells.

Original languageEnglish (US)
Pages (from-to)11930-11935
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number26
DOIs
StatePublished - Jun 29 2010

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Histone Code
Germinal Center
B-Lymphocytes
CpG Islands
Cell Line
Untranslated RNA
Genetic Translocation
Histones
Lysine
Chromosomes
Gene Expression

Keywords

  • ChIP-on-chip
  • Chromatin structure
  • DNA looping
  • Epigenetic
  • Transcriptional regulation

ASJC Scopus subject areas

  • General

Cite this

BCL6 promoter interacts with far upstream sequences with greatly enhanced activating histone modifications in germinal center B cells. / Ramachandrareddy, Himabindu; Bouska, Alyssa; Shen, Yulei; Ji, Ming; Rizzino, A Angie; Chan, Wing C.; McKeithan, Timothy W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 26, 29.06.2010, p. 11930-11935.

Research output: Contribution to journalArticle

Ramachandrareddy, Himabindu ; Bouska, Alyssa ; Shen, Yulei ; Ji, Ming ; Rizzino, A Angie ; Chan, Wing C. ; McKeithan, Timothy W. / BCL6 promoter interacts with far upstream sequences with greatly enhanced activating histone modifications in germinal center B cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2010 ; Vol. 107, No. 26. pp. 11930-11935.
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