HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres

Muhammad Shuaib, Khalid Ouararhni, Stefan Dimitrov, Ali Hamiche

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

The human histone H3 variant, CENP-A, replaces the conventional histone H3 in centromeric chromatin and, together with centromere-specific DNA-binding factors, directs the assembly of the kinetochore. We purified the prenucelosomal e-CENP-A complex. We found that HJURP, a member of the complex, was required for cell cycle specific targeting of CENP-A to centromeres. HJURP facilitated efficient deposition of CENP-A/H4 tetramers to naked DNA in vitro. Bacterially expressed HJURP binds at a stoichiometric ratio tothe CENP-A/H4 tetramer but not to the H3/H4 tetramer. The binding occurred through a conserved HJURP short N-terminal domain, termed CBD. The novel characteristic identified in vertebrates that we named TLTY box of CBD, was essential for formation of the HJURP-CENP-A/H4 complex. Our data identified HJURP as a vertebrate CENP-A chaperone and dissected its mode of interactions with CENP-A.

Original languageEnglish
Pages (from-to)1349-1354
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number4
DOIs
Publication statusPublished - 26 Jan 2010
Externally publishedYes

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Centromere
Histones
Vertebrates
Kinetochores
centromere protein A
DNA
Chromatin
Cell Cycle

Keywords

  • Histone chaperone
  • Histone variant

ASJC Scopus subject areas

  • General

Cite this

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T1 - HJURP binds CENP-A via a highly conserved N-terminal domain and mediates its deposition at centromeres

AU - Shuaib, Muhammad

AU - Ouararhni, Khalid

AU - Dimitrov, Stefan

AU - Hamiche, Ali

PY - 2010/1/26

Y1 - 2010/1/26

N2 - The human histone H3 variant, CENP-A, replaces the conventional histone H3 in centromeric chromatin and, together with centromere-specific DNA-binding factors, directs the assembly of the kinetochore. We purified the prenucelosomal e-CENP-A complex. We found that HJURP, a member of the complex, was required for cell cycle specific targeting of CENP-A to centromeres. HJURP facilitated efficient deposition of CENP-A/H4 tetramers to naked DNA in vitro. Bacterially expressed HJURP binds at a stoichiometric ratio tothe CENP-A/H4 tetramer but not to the H3/H4 tetramer. The binding occurred through a conserved HJURP short N-terminal domain, termed CBD. The novel characteristic identified in vertebrates that we named TLTY box of CBD, was essential for formation of the HJURP-CENP-A/H4 complex. Our data identified HJURP as a vertebrate CENP-A chaperone and dissected its mode of interactions with CENP-A.

AB - The human histone H3 variant, CENP-A, replaces the conventional histone H3 in centromeric chromatin and, together with centromere-specific DNA-binding factors, directs the assembly of the kinetochore. We purified the prenucelosomal e-CENP-A complex. We found that HJURP, a member of the complex, was required for cell cycle specific targeting of CENP-A to centromeres. HJURP facilitated efficient deposition of CENP-A/H4 tetramers to naked DNA in vitro. Bacterially expressed HJURP binds at a stoichiometric ratio tothe CENP-A/H4 tetramer but not to the H3/H4 tetramer. The binding occurred through a conserved HJURP short N-terminal domain, termed CBD. The novel characteristic identified in vertebrates that we named TLTY box of CBD, was essential for formation of the HJURP-CENP-A/H4 complex. Our data identified HJURP as a vertebrate CENP-A chaperone and dissected its mode of interactions with CENP-A.

KW - Histone chaperone

KW - Histone variant

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