TY - JOUR
T1 - Sensitive effect of linker histone binding mode and subtype on chromatin condensation
AU - Perisic, Ognjen
AU - Portillo-Ledesma, Stephanie
AU - Schlick, Tamar
N1 - Funding Information:
National Institute of General Medical Sciences [R35GM122562]; Philip Morris and Philip Morris International (to T. S.). Funding for open access charge: National Institute of General Medical Sciences (to T.S.). Conflict of interest statement. None declared.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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.
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U2 - 10.1093/nar/gkz234
DO - 10.1093/nar/gkz234
M3 - Article
C2 - 30968131
AN - SCOPUS:85067217255
SN - 0305-1048
VL - 47
SP - 4948
EP - 4957
JO - Nucleic acids research
JF - Nucleic acids research
IS - 10
ER -