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Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation

The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is r...

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Autores principales: Zheng, Sanduo, Villa, Raffaella, Wang, Jia, Feng, Yingang, Wang, Jinfeng, Becker, Peter B., Ye, Keqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248295/
https://www.ncbi.nlm.nih.gov/pubmed/25452275
http://dx.doi.org/10.1101/gad.250936.114
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author Zheng, Sanduo
Villa, Raffaella
Wang, Jia
Feng, Yingang
Wang, Jinfeng
Becker, Peter B.
Ye, Keqiong
author_facet Zheng, Sanduo
Villa, Raffaella
Wang, Jia
Feng, Yingang
Wang, Jinfeng
Becker, Peter B.
Ye, Keqiong
author_sort Zheng, Sanduo
collection PubMed
description The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is recognized remains unknown. Here, we identified the CXC domain of MSL2 specifically recognizing the MRE motif and determined its crystal structure bound to specific and nonspecific DNAs. The CXC domain primarily contacts one strand of DNA duplex and employs a single arginine to directly read out dinucleotide sequences from the minor groove. The arginine is flexible when bound to nonspecific sequences. The core region of the MRE motif harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants of MSL2 are impaired in MRE binding and X chromosome localization in vivo. Our results reveal multiple dynamic DNA-binding modes of the CXC domain that target the MSL-DCC to X chromosomes.
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spelling pubmed-42482952015-06-01 Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation Zheng, Sanduo Villa, Raffaella Wang, Jia Feng, Yingang Wang, Jinfeng Becker, Peter B. Ye, Keqiong Genes Dev Research Paper The male-specific lethal dosage compensation complex (MSL-DCC) selectively assembles on the X chromosome in Drosophila males and activates gene transcription by twofold through histone acetylation. An MSL recognition element (MRE) sequence motif nucleates the initial MSL association, but how it is recognized remains unknown. Here, we identified the CXC domain of MSL2 specifically recognizing the MRE motif and determined its crystal structure bound to specific and nonspecific DNAs. The CXC domain primarily contacts one strand of DNA duplex and employs a single arginine to directly read out dinucleotide sequences from the minor groove. The arginine is flexible when bound to nonspecific sequences. The core region of the MRE motif harbors two binding sites on opposite strands that can cooperatively recruit a CXC dimer. Specific DNA-binding mutants of MSL2 are impaired in MRE binding and X chromosome localization in vivo. Our results reveal multiple dynamic DNA-binding modes of the CXC domain that target the MSL-DCC to X chromosomes. Cold Spring Harbor Laboratory Press 2014-12-01 /pmc/articles/PMC4248295/ /pubmed/25452275 http://dx.doi.org/10.1101/gad.250936.114 Text en © 2014 Zheng et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Zheng, Sanduo
Villa, Raffaella
Wang, Jia
Feng, Yingang
Wang, Jinfeng
Becker, Peter B.
Ye, Keqiong
Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation
title Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation
title_full Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation
title_fullStr Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation
title_full_unstemmed Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation
title_short Structural basis of X chromosome DNA recognition by the MSL2 CXC domain during Drosophila dosage compensation
title_sort structural basis of x chromosome dna recognition by the msl2 cxc domain during drosophila dosage compensation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248295/
https://www.ncbi.nlm.nih.gov/pubmed/25452275
http://dx.doi.org/10.1101/gad.250936.114
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