Affiliation:
1. Department of Cellular Biology, University of Georgia, Athens, Georgia, USA
Abstract
ABSTRACT
Chromatin boundary elements (CBEs) are widely distributed in the genome and mediate formation of chromatin loops, but their roles in gene regulation remain poorly understood. The complex expression pattern of the
Drosophila
homeotic gene
Sex combs reduced
(
Scr
) is directed by an unusually long regulatory sequence harboring diverse
cis
elements and an intervening neighbor gene
fushi tarazu
(
ftz
). Here we report the presence of a multitude of CBEs in the
Scr
regulatory region. Selective and dynamic pairing among these CBEs mediates developmentally regulated chromatin loops. In particular, the SF1 boundary plays a central role in organizing two subsets of chromatin loops: one subset encloses
ftz
, limiting its access by the surrounding
Scr
enhancers and compartmentalizing distinct histone modifications, and the other subset subdivides the
Scr
regulatory sequences into independent enhancer access domains. We show that these CBEs exhibit diverse enhancer-blocking activities that vary in strength and tissue distribution. Tandem pairing of SF1 and SF2, two strong CBEs that flank the
ftz
domain, allows the distal enhancers to bypass their block in transgenic
Drosophila
, providing a mechanism for the endogenous
Scr
enhancer to circumvent the
ftz
domain. Our study demonstrates how an endogenous CBE network, centrally orchestrated by SF1, could remodel the genomic environment to facilitate gene regulation during development.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Cited by
14 articles.
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