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

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 approximately 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.

authors

Ramachandrareddy H,Bouska A,Shen Y,Ji M,Rizzino A,Chan WC,McKeithan TW

doi

10.1073/pnas.1004962107

subject

Has Abstract

pub_date

2010-06-29 00:00:00

pages

11930-5

issue

26

eissn

0027-8424

issn

1091-6490

pii

1004962107

journal_volume

107

pub_type

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