A capped Tudor domain within a core subunit of the Sin3L/Rpd3L histone deacetylase complex binds to nucleic acid G-quadruplexes

Ryan Dale Marcum, Joseph Hsieh, Maksim Giljen, Emily Justice, Nicolas Daffern, Yongbo Zhang, Ishwar Radhakrishnan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Chromatin-modifying complexes containing histone deacetylase (HDAC) activities play critical roles in the regulation of gene transcription in eukaryotes. These complexes are thought to lack intrinsic DNA-binding activity, but according to a well-established paradigm, they are recruited via protein–protein interactions by gene-specific transcription factors and posttranslational histone modifications to their sites of action on the genome. The mammalian Sin3L/Rpd3L complex, comprising more than a dozen different polypeptides, is an ancient HDAC complex found in diverse eukaryotes. The subunits of this complex harbor conserved domains and motifs of unknown structure and function. Here, we show that Sds3, a constitutively-associated subunit critical for the proper functioning of the Sin3L/Rpd3L complex, harbors a type of Tudor domain that we designate the capped Tudor domain. Unlike canonical Tudor domains that bind modified histones, the Sds3 capped Tudor domain binds to nucleic acids that can form higher-order structures such as G-quadruplexes and shares similarities with the knotted Tudor domain of the Esa1 histone acetyltransferase that was previously shown to bind single-stranded RNA. Our findings expand the range of macromolecules capable of recruiting the Sin3L/Rpd3L complex and draw attention to potentially new biological roles for this HDAC complex.

Original languageEnglish (US)
Article number101558
JournalJournal of Biological Chemistry
Volume298
Issue number2
DOIs
StatePublished - Feb 1 2022

Funding

Funding and additional information—This work was supported by grants from the American Heart Association to I. R. (17GRNT33680167) and R. D. M. (16PRE27260041) and to Northwestern University for providing J. H., M. G., and E. J. with funds for undergraduate research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Acknowledgments—This work was supported by grants from the National Institutes of Health for upgrading the 600 MHz NMR console (S10 OD012016). We thank Arabela Grigorescu in the Keck Biophysics Facility for assistance with ITC measurements and members of the Radhakrishnan lab for critical comments. We are grateful to the Robert H. Lurie Comprehensive Cancer Center at Northwestern for supporting structural biology research. We thank Yawen Bai at the NCI for providing the plasmid encoding histone H2A-H2B heterodimer.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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