Weakly positioned nucleosomes enhance the transcriptional competency of chromatin

Yaakov Belch, Jingyi Yang, Yang Liu, Sridhar A. Malkaram, Rong Liu, Jean Jack M. Riethoven, Istvan Ladunga

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Transcription is affected by nucleosomal resistance against polymerase passage. In turn, nucleosomal resistance is determined by DNA sequence, histone chaperones and remodeling enzymes. The contributions of these factors are widely debated: one recent title claims '... DNA-encoded nucleosome organization...' while another title states that ''histone-DNA interactions are not the major determinant of nucleosome positions.'' These opposing conclusions were drawn from similar experiments analyzed by idealized methods. We attempt to resolve this controversy to reveal nucleosomal competency for transcription. Methodology/Principal Findings:To this end, we analyzed 26 in vivo, nonlinked, and in vitro genome-wide nucleosome maps/replicates by new, rigorous methods. Individual H2A nucleosomes are reconstituted inaccurately by transcription, chaperones and remodeling enzymes. At gene centers, weakly positioned nucleosome arrays facilitate rapid histone eviction and remodeling, easing polymerase passage. Fuzzy positioning is not due to artefacts. At the regional level, transcriptional competency is strongly influenced by intrinsic histone-DNA affinities. This is confirmed by reproducing the high in vivo occupancy of translated regions and the low occupancy of intergenic regions in reconstitutions from purified DNA and histones. Regional level occupancy patterns are protected from invading histones by nucleosome excluding sequences and barrier nucleosomes at gene boundaries and within genes. Conclusions/Significance:Dense arrays of weakly positioned nucleosomes appear to be necessary for transcription. Weak positioning at exons facilitates temporary remodeling, polymerase passage and hence the competency for transcription. At regional levels, the DNA sequence plays a major role in determining these features but positions of individual nucleosomes are typically modified by transcription, chaperones and enzymes. This competency is reduced at intergenic regions by sequence features, barrier nucleosomes, and proteins, preventing accessibility regulation of untargeted genes. This combination of DNA- and protein-influenced positioning regulates DNA accessibility and competence for regulatory protein binding and transcription. Interactive nucleosome displays are offered at http://chromatin.unl.edu/cgi-bin/skyline.cgi.

Original languageEnglish (US)
Article numbere12984
JournalPloS one
Volume5
Issue number9
DOIs
StatePublished - Nov 1 2010

Fingerprint

nucleosomes
Nucleosomes
Chromatin
chromatin
Transcription
histones
transcription (genetics)
Histones
Genes
Intergenic DNA
DNA
DNA sequences
intergenic DNA
Enzymes
genes
Histone Chaperones
enzymes
nucleotide sequences
protein binding
regulatory proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Weakly positioned nucleosomes enhance the transcriptional competency of chromatin. / Belch, Yaakov; Yang, Jingyi; Liu, Yang; Malkaram, Sridhar A.; Liu, Rong; Riethoven, Jean Jack M.; Ladunga, Istvan.

In: PloS one, Vol. 5, No. 9, e12984, 01.11.2010.

Research output: Contribution to journalArticle

Belch, Yaakov ; Yang, Jingyi ; Liu, Yang ; Malkaram, Sridhar A. ; Liu, Rong ; Riethoven, Jean Jack M. ; Ladunga, Istvan. / Weakly positioned nucleosomes enhance the transcriptional competency of chromatin. In: PloS one. 2010 ; Vol. 5, No. 9.
@article{17d0b6ead7694b5fa41e4d2ae9cd0979,
title = "Weakly positioned nucleosomes enhance the transcriptional competency of chromatin",
abstract = "Background: Transcription is affected by nucleosomal resistance against polymerase passage. In turn, nucleosomal resistance is determined by DNA sequence, histone chaperones and remodeling enzymes. The contributions of these factors are widely debated: one recent title claims '... DNA-encoded nucleosome organization...' while another title states that ''histone-DNA interactions are not the major determinant of nucleosome positions.'' These opposing conclusions were drawn from similar experiments analyzed by idealized methods. We attempt to resolve this controversy to reveal nucleosomal competency for transcription. Methodology/Principal Findings:To this end, we analyzed 26 in vivo, nonlinked, and in vitro genome-wide nucleosome maps/replicates by new, rigorous methods. Individual H2A nucleosomes are reconstituted inaccurately by transcription, chaperones and remodeling enzymes. At gene centers, weakly positioned nucleosome arrays facilitate rapid histone eviction and remodeling, easing polymerase passage. Fuzzy positioning is not due to artefacts. At the regional level, transcriptional competency is strongly influenced by intrinsic histone-DNA affinities. This is confirmed by reproducing the high in vivo occupancy of translated regions and the low occupancy of intergenic regions in reconstitutions from purified DNA and histones. Regional level occupancy patterns are protected from invading histones by nucleosome excluding sequences and barrier nucleosomes at gene boundaries and within genes. Conclusions/Significance:Dense arrays of weakly positioned nucleosomes appear to be necessary for transcription. Weak positioning at exons facilitates temporary remodeling, polymerase passage and hence the competency for transcription. At regional levels, the DNA sequence plays a major role in determining these features but positions of individual nucleosomes are typically modified by transcription, chaperones and enzymes. This competency is reduced at intergenic regions by sequence features, barrier nucleosomes, and proteins, preventing accessibility regulation of untargeted genes. This combination of DNA- and protein-influenced positioning regulates DNA accessibility and competence for regulatory protein binding and transcription. Interactive nucleosome displays are offered at http://chromatin.unl.edu/cgi-bin/skyline.cgi.",
author = "Yaakov Belch and Jingyi Yang and Yang Liu and Malkaram, {Sridhar A.} and Rong Liu and Riethoven, {Jean Jack M.} and Istvan Ladunga",
year = "2010",
month = "11",
day = "1",
doi = "10.1371/journal.pone.0012984",
language = "English (US)",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

TY - JOUR

T1 - Weakly positioned nucleosomes enhance the transcriptional competency of chromatin

AU - Belch, Yaakov

AU - Yang, Jingyi

AU - Liu, Yang

AU - Malkaram, Sridhar A.

AU - Liu, Rong

AU - Riethoven, Jean Jack M.

AU - Ladunga, Istvan

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background: Transcription is affected by nucleosomal resistance against polymerase passage. In turn, nucleosomal resistance is determined by DNA sequence, histone chaperones and remodeling enzymes. The contributions of these factors are widely debated: one recent title claims '... DNA-encoded nucleosome organization...' while another title states that ''histone-DNA interactions are not the major determinant of nucleosome positions.'' These opposing conclusions were drawn from similar experiments analyzed by idealized methods. We attempt to resolve this controversy to reveal nucleosomal competency for transcription. Methodology/Principal Findings:To this end, we analyzed 26 in vivo, nonlinked, and in vitro genome-wide nucleosome maps/replicates by new, rigorous methods. Individual H2A nucleosomes are reconstituted inaccurately by transcription, chaperones and remodeling enzymes. At gene centers, weakly positioned nucleosome arrays facilitate rapid histone eviction and remodeling, easing polymerase passage. Fuzzy positioning is not due to artefacts. At the regional level, transcriptional competency is strongly influenced by intrinsic histone-DNA affinities. This is confirmed by reproducing the high in vivo occupancy of translated regions and the low occupancy of intergenic regions in reconstitutions from purified DNA and histones. Regional level occupancy patterns are protected from invading histones by nucleosome excluding sequences and barrier nucleosomes at gene boundaries and within genes. Conclusions/Significance:Dense arrays of weakly positioned nucleosomes appear to be necessary for transcription. Weak positioning at exons facilitates temporary remodeling, polymerase passage and hence the competency for transcription. At regional levels, the DNA sequence plays a major role in determining these features but positions of individual nucleosomes are typically modified by transcription, chaperones and enzymes. This competency is reduced at intergenic regions by sequence features, barrier nucleosomes, and proteins, preventing accessibility regulation of untargeted genes. This combination of DNA- and protein-influenced positioning regulates DNA accessibility and competence for regulatory protein binding and transcription. Interactive nucleosome displays are offered at http://chromatin.unl.edu/cgi-bin/skyline.cgi.

AB - Background: Transcription is affected by nucleosomal resistance against polymerase passage. In turn, nucleosomal resistance is determined by DNA sequence, histone chaperones and remodeling enzymes. The contributions of these factors are widely debated: one recent title claims '... DNA-encoded nucleosome organization...' while another title states that ''histone-DNA interactions are not the major determinant of nucleosome positions.'' These opposing conclusions were drawn from similar experiments analyzed by idealized methods. We attempt to resolve this controversy to reveal nucleosomal competency for transcription. Methodology/Principal Findings:To this end, we analyzed 26 in vivo, nonlinked, and in vitro genome-wide nucleosome maps/replicates by new, rigorous methods. Individual H2A nucleosomes are reconstituted inaccurately by transcription, chaperones and remodeling enzymes. At gene centers, weakly positioned nucleosome arrays facilitate rapid histone eviction and remodeling, easing polymerase passage. Fuzzy positioning is not due to artefacts. At the regional level, transcriptional competency is strongly influenced by intrinsic histone-DNA affinities. This is confirmed by reproducing the high in vivo occupancy of translated regions and the low occupancy of intergenic regions in reconstitutions from purified DNA and histones. Regional level occupancy patterns are protected from invading histones by nucleosome excluding sequences and barrier nucleosomes at gene boundaries and within genes. Conclusions/Significance:Dense arrays of weakly positioned nucleosomes appear to be necessary for transcription. Weak positioning at exons facilitates temporary remodeling, polymerase passage and hence the competency for transcription. At regional levels, the DNA sequence plays a major role in determining these features but positions of individual nucleosomes are typically modified by transcription, chaperones and enzymes. This competency is reduced at intergenic regions by sequence features, barrier nucleosomes, and proteins, preventing accessibility regulation of untargeted genes. This combination of DNA- and protein-influenced positioning regulates DNA accessibility and competence for regulatory protein binding and transcription. Interactive nucleosome displays are offered at http://chromatin.unl.edu/cgi-bin/skyline.cgi.

UR - http://www.scopus.com/inward/record.url?scp=77958537326&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77958537326&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0012984

DO - 10.1371/journal.pone.0012984

M3 - Article

C2 - 20886052

AN - SCOPUS:77958537326

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e12984

ER -