Molecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC

Cynthia Tallant, Erica Valentini, Oleg Fedorov, Lois Overvoorde, Fleur M. Ferguson, Panagis Filippakopoulos, Dmitri I. Svergun, Stefan Knapp, Alessio Ciulli (Lead / Corresponding author)

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex.

Original languageEnglish
Pages (from-to)80-92
Number of pages13
JournalStructure
Volume23
Issue number1
DOIs
Publication statusPublished - 6 Jan 2015

Fingerprint

Chromatin Assembly and Disassembly
Histones
Fingers
Tail
Acetylation
Ribosomal DNA
Complementary RNA
Nucleosomes
Zinc Fingers
Post Translational Protein Processing
Chromatin

Keywords

  • Amino acid sequence
  • Chromatin assembly and disassembly
  • Chromosomal proteins, Non-histone
  • Histones
  • Humans
  • Models, Molecular
  • Molecular sequence data
  • Protein binding
  • Protein interaction domains and motifs
  • Protein structure, Quaternary
  • Sequence homology, Amino acid
  • Zinc fingers

Cite this

Tallant, Cynthia ; Valentini, Erica ; Fedorov, Oleg ; Overvoorde, Lois ; Ferguson, Fleur M. ; Filippakopoulos, Panagis ; Svergun, Dmitri I. ; Knapp, Stefan ; Ciulli, Alessio. / Molecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC. In: Structure. 2015 ; Vol. 23, No. 1. pp. 80-92.
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abstract = "Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex.",
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Tallant, C, Valentini, E, Fedorov, O, Overvoorde, L, Ferguson, FM, Filippakopoulos, P, Svergun, DI, Knapp, S & Ciulli, A 2015, 'Molecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC', Structure, vol. 23, no. 1, pp. 80-92. https://doi.org/10.1016/j.str.2014.10.017

Molecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC. / Tallant, Cynthia; Valentini, Erica; Fedorov, Oleg; Overvoorde, Lois; Ferguson, Fleur M.; Filippakopoulos, Panagis; Svergun, Dmitri I.; Knapp, Stefan; Ciulli, Alessio (Lead / Corresponding author).

In: Structure, Vol. 23, No. 1, 06.01.2015, p. 80-92.

Research output: Contribution to journalArticle

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T1 - Molecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC

AU - Tallant, Cynthia

AU - Valentini, Erica

AU - Fedorov, Oleg

AU - Overvoorde, Lois

AU - Ferguson, Fleur M.

AU - Filippakopoulos, Panagis

AU - Svergun, Dmitri I.

AU - Knapp, Stefan

AU - Ciulli, Alessio

N1 - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2015/1/6

Y1 - 2015/1/6

N2 - Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex.

AB - Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex.

KW - Amino acid sequence

KW - Chromatin assembly and disassembly

KW - Chromosomal proteins, Non-histone

KW - Histones

KW - Humans

KW - Models, Molecular

KW - Molecular sequence data

KW - Protein binding

KW - Protein interaction domains and motifs

KW - Protein structure, Quaternary

KW - Sequence homology, Amino acid

KW - Zinc fingers

U2 - 10.1016/j.str.2014.10.017

DO - 10.1016/j.str.2014.10.017

M3 - Article

C2 - 25533489

VL - 23

SP - 80

EP - 92

JO - Structure

JF - Structure

SN - 0969-2126

IS - 1

ER -