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J Cell Sci. 2019 Mar 8;132(5). pii: jcs226092. doi: 10.1242/jcs.226092.

The zinc-finger protein CLAMP promotes gypsy chromatin insulator function in Drosophila.

Author information

1
Nuclear Organization and Gene Expression Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
3
Nuclear Organization and Gene Expression Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA leielissa@niddk.nih.gov.

Abstract

Chromatin insulators are DNA-protein complexes that establish independent higher-order DNA domains to influence transcription. Insulators are functionally defined by two properties: they can block communication between an enhancer and a promoter, and also act as a barrier between heterochromatin and euchromatin. In Drosophila, the gypsy insulator complex contains three core components; Su(Hw), CP190 and Mod(mdg4)67.2. Here, we identify a novel role for Chromatin-linked adaptor for MSL proteins (CLAMP) in promoting gypsy chromatin insulator function. When clamp is knocked down, gypsy-dependent enhancer-blocking and barrier activities are strongly reduced. CLAMP associates physically with the core gypsy insulator complex, and ChIP-seq analysis reveals extensive overlap, particularly with promoter-bound CP190 on chromatin. Depletion of CLAMP disrupts CP190 binding at a minority of shared sites, whereas depletion of CP190 results in extensive loss of CLAMP chromatin association. Finally, reduction of CLAMP disrupts CP190 localization within the nucleus. Our results support a positive functional relationship between CLAMP and CP190 to promote gypsy chromatin insulator activity.

KEYWORDS:

Barrier activity; CLAMP; CP190; Chromatin insulator; Enhancer blocking; Insulator bodies; gypsy

PMID:
30718365
PMCID:
PMC6432716
[Available on 2020-03-01]
DOI:
10.1242/jcs.226092
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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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