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Active and Inactive Enhancers Cooperate to Exert Localized and Long-Range Control
of Gene Regulation
#MMPMID27239026
Proudhon C
; Snetkova V
; Raviram R
; Lobry C
; Badri S
; Jiang T
; Hao B
; Trimarchi T
; Kluger Y
; Aifantis I
; Bonneau R
; Skok JA
Cell Rep
2016[Jun]; 15
(10
): 2159-2169
PMID27239026
show ga
V(D)J recombination relies on the presence of proximal enhancers that activate
the antigen receptor (AgR) loci in a lineage- and stage-specific manner.
Unexpectedly, we find that both active and inactive AgR enhancers cooperate to
disseminate their effects in a localized and long-range manner. Here, we
demonstrate the importance of short-range contacts between active enhancers that
constitute an Igk super-enhancer in B cells. Deletion of one element reduces the
interaction frequency between other enhancers in the hub, which compromises the
transcriptional output of each component. Furthermore, we establish that, in
T cells, long-range contact and cooperation between the inactive Igk enhancer
MiE? and the active Tcrb enhancer E? alters enrichment of CBF? binding in a
manner that impacts Tcrb recombination. These findings underline the complexities
of enhancer regulation and point to a role for localized and long-range
enhancer-sharing between active and inactive elements in lineage- and
stage-specific control.
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