DNA sequence influences hexasome orientation to regulate DNA accessibility.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
20 06 2019
20 06 2019
Historique:
accepted:
20
04
2019
revised:
03
04
2019
received:
17
02
2019
entrez:
20
6
2019
pubmed:
20
6
2019
medline:
26
11
2019
Statut:
ppublish
Résumé
Nucleosomes, the fundamental organizing units of eukaryotic genomes, contain ∼146 base pairs of DNA wrapped around a histone H3-H4 tetramer and two histone H2A-H2B dimers. Converting nucleosomes into hexasomes by removal of a H2A-H2B dimer is an important regulatory event, but its regulation and functional consequences are not well-understood. To investigate the influence of hexasomes on DNA accessibility, we used the property of the Widom-601 Nucleosome Positioning Sequence (NPS) to form homogeneously oriented hexasomes in vitro. We find that DNA accessibility to transcription factors (TF) on the hexasome H2A-H2B distal side is identical to naked DNA, while the accessibility on the H2A-H2B proximal side is reduced by 2-fold, which is due to a 2-fold reduction in hexasome unwrapping probability. We then determined that a 23 bp region of the Widom-601 NPS is responsible for forming homogeneously oriented hexasomes. Analysis of published ChIP-exo data of hexasome containing genes identified two DNA sequence motifs that correlate with hexasome orientation in vivo, while ExoIII mapping studies of these sequences revealed they generate homogeneously oriented hexasomes in vitro. These results indicate that hexasome orientation, which is influenced by the underlying DNA sequence in vivo, is important for modulating DNA accessibility to regulate transcription.
Identifiants
pubmed: 31216039
pii: 5477456
doi: 10.1093/nar/gkz283
pmc: PMC6582347
doi:
Substances chimiques
DNA-Binding Proteins
0
Histones
0
Nucleosomes
0
Transcription Factors
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
5617-5633Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM121966
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM131626
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI127582
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM086252
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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