Sensitive effect of linker histone binding mode and subtype on chromatin condensation

Ognjen Perišić, Stephanie Portillo-Ledesma, Tamar Schlick

Research output: Contribution to journalArticle

Abstract

The complex role of linker histone (LH) on chromatin compaction regulation has been highlighted by recent discoveries of the effect of LH binding variability and isoforms on genome structure and function. Here we examine the effect of two LH variants and variable binding modes on the structure of chromatin fibers. Our mesoscale modeling considers oligonucleosomes with H1C and H1E, bound in three different on and off-dyad modes, and spanning different LH densities (0.5-1.6 per nucleosome), over a wide range of physiologically relevant nucleosome repeat lengths (NRLs). Our studies reveal an LH-variant and binding-mode dependent heterogeneous ensemble of fiber structures with variable packing ratios, sedimentation coefficients, and persistence lengths. For maximal compaction, besides dominantly interacting with parental DNA, LHs must have strong interactions with nonparental DNA and promote tail/nonparental core interactions. An off-dyad binding of H1E enables both; others compromise compaction for bendability. We also find that an increase of LH density beyond 1 is best accommodated in chromatosomes with one on-dyad and one off-dyad LH. We suggest that variable LH binding modes and concentrations are advantageous, allowing tunable levels of chromatin condensation and DNA accessibility/interactions. Thus, LHs add another level of epigenetic regulation of chromatin.

Original languageEnglish (US)
Pages (from-to)4948-4957
Number of pages10
JournalNucleic acids research
Volume47
Issue number10
DOIs
StatePublished - Jun 4 2019

Fingerprint

Histones
Chromatin
Nucleosomes
DNA
Epigenomics
Protein Isoforms
Genome

ASJC Scopus subject areas

  • Genetics

Cite this

Sensitive effect of linker histone binding mode and subtype on chromatin condensation. / Perišić, Ognjen; Portillo-Ledesma, Stephanie; Schlick, Tamar.

In: Nucleic acids research, Vol. 47, No. 10, 04.06.2019, p. 4948-4957.

Research output: Contribution to journalArticle

Perišić, Ognjen ; Portillo-Ledesma, Stephanie ; Schlick, Tamar. / Sensitive effect of linker histone binding mode and subtype on chromatin condensation. In: Nucleic acids research. 2019 ; Vol. 47, No. 10. pp. 4948-4957.
@article{374a4f719885482c8f74f183e44d941d,
title = "Sensitive effect of linker histone binding mode and subtype on chromatin condensation",
abstract = "The complex role of linker histone (LH) on chromatin compaction regulation has been highlighted by recent discoveries of the effect of LH binding variability and isoforms on genome structure and function. Here we examine the effect of two LH variants and variable binding modes on the structure of chromatin fibers. Our mesoscale modeling considers oligonucleosomes with H1C and H1E, bound in three different on and off-dyad modes, and spanning different LH densities (0.5-1.6 per nucleosome), over a wide range of physiologically relevant nucleosome repeat lengths (NRLs). Our studies reveal an LH-variant and binding-mode dependent heterogeneous ensemble of fiber structures with variable packing ratios, sedimentation coefficients, and persistence lengths. For maximal compaction, besides dominantly interacting with parental DNA, LHs must have strong interactions with nonparental DNA and promote tail/nonparental core interactions. An off-dyad binding of H1E enables both; others compromise compaction for bendability. We also find that an increase of LH density beyond 1 is best accommodated in chromatosomes with one on-dyad and one off-dyad LH. We suggest that variable LH binding modes and concentrations are advantageous, allowing tunable levels of chromatin condensation and DNA accessibility/interactions. Thus, LHs add another level of epigenetic regulation of chromatin.",
author = "Ognjen Perišić and Stephanie Portillo-Ledesma and Tamar Schlick",
year = "2019",
month = "6",
day = "4",
doi = "10.1093/nar/gkz234",
language = "English (US)",
volume = "47",
pages = "4948--4957",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "10",

}

TY - JOUR

T1 - Sensitive effect of linker histone binding mode and subtype on chromatin condensation

AU - Perišić, Ognjen

AU - Portillo-Ledesma, Stephanie

AU - Schlick, Tamar

PY - 2019/6/4

Y1 - 2019/6/4

N2 - The complex role of linker histone (LH) on chromatin compaction regulation has been highlighted by recent discoveries of the effect of LH binding variability and isoforms on genome structure and function. Here we examine the effect of two LH variants and variable binding modes on the structure of chromatin fibers. Our mesoscale modeling considers oligonucleosomes with H1C and H1E, bound in three different on and off-dyad modes, and spanning different LH densities (0.5-1.6 per nucleosome), over a wide range of physiologically relevant nucleosome repeat lengths (NRLs). Our studies reveal an LH-variant and binding-mode dependent heterogeneous ensemble of fiber structures with variable packing ratios, sedimentation coefficients, and persistence lengths. For maximal compaction, besides dominantly interacting with parental DNA, LHs must have strong interactions with nonparental DNA and promote tail/nonparental core interactions. An off-dyad binding of H1E enables both; others compromise compaction for bendability. We also find that an increase of LH density beyond 1 is best accommodated in chromatosomes with one on-dyad and one off-dyad LH. We suggest that variable LH binding modes and concentrations are advantageous, allowing tunable levels of chromatin condensation and DNA accessibility/interactions. Thus, LHs add another level of epigenetic regulation of chromatin.

AB - The complex role of linker histone (LH) on chromatin compaction regulation has been highlighted by recent discoveries of the effect of LH binding variability and isoforms on genome structure and function. Here we examine the effect of two LH variants and variable binding modes on the structure of chromatin fibers. Our mesoscale modeling considers oligonucleosomes with H1C and H1E, bound in three different on and off-dyad modes, and spanning different LH densities (0.5-1.6 per nucleosome), over a wide range of physiologically relevant nucleosome repeat lengths (NRLs). Our studies reveal an LH-variant and binding-mode dependent heterogeneous ensemble of fiber structures with variable packing ratios, sedimentation coefficients, and persistence lengths. For maximal compaction, besides dominantly interacting with parental DNA, LHs must have strong interactions with nonparental DNA and promote tail/nonparental core interactions. An off-dyad binding of H1E enables both; others compromise compaction for bendability. We also find that an increase of LH density beyond 1 is best accommodated in chromatosomes with one on-dyad and one off-dyad LH. We suggest that variable LH binding modes and concentrations are advantageous, allowing tunable levels of chromatin condensation and DNA accessibility/interactions. Thus, LHs add another level of epigenetic regulation of chromatin.

UR - http://www.scopus.com/inward/record.url?scp=85067217255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067217255&partnerID=8YFLogxK

U2 - 10.1093/nar/gkz234

DO - 10.1093/nar/gkz234

M3 - Article

VL - 47

SP - 4948

EP - 4957

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 10

ER -