Regulatory modules function in a non-autonomous manner to control transcription of the mbp gene.

Abstract:

:Multiple regulatory modules contribute to the complex expression programs realized by many loci. Although long thought of as isolated components, recent studies demonstrate that such regulatory sequences can physically associate with promoters and with each other and may localize to specific sub-nuclear transcription factories. These associations provide a substrate for putative interactions and have led to the suggested existence of a transcriptional interactome. Here, using a controlled strategy of transgenesis, we analyzed the functional consequences of regulatory sequence interaction within the myelin basic protein (mbp) locus. Interactions were revealed through comparisons of the qualitative and quantitative expression programs conferred by an allelic series of 11 different enhancer/inter-enhancer combinations ligated to a common promoter/reporter gene. In a developmentally contextual manner, the regulatory output of all modules changed markedly in the presence of other sequences. Predicted by transgene expression programs, deletion of one such module from the endogenous locus reduced oligodendrocyte expression levels but unexpectedly, also attenuated expression of the overlapping golli transcriptional unit. These observations support a regulatory architecture that extends beyond a combinatorial model to include frequent interactions capable of significantly modulating the functions conferred through regulatory modules in isolation.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Dib S,Denarier E,Dionne N,Beaudoin M,Friedman HH,Peterson AC

doi

10.1093/nar/gkq1160

subject

Has Abstract

pub_date

2011-04-01 00:00:00

pages

2548-58

issue

7

eissn

0305-1048

issn

1362-4962

pii

gkq1160

journal_volume

39

pub_type

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