We elucidated how the conserved elongation
factors facilitate efficient RNAPII passage through
a nucleosome (Fig. 4). This may better represent
the transcription of gene-body nucleosomes be-
cause Spt4/5 and Elf1 associate with elongating
RNAPII ( 11 ). In the cellular context, EC cooper-
ates with the other elongation factors, histone
chaperones, and nucleosome remodelers, which
could help relieve the nucleosomal barriers. The
observed partially DNA-peeled nucleosome at
SHL(–1) or SHL(–5) should provide a platform
for various chromatin functions associated with
thesefactors.Bycontrast,thepromoter-proximal,
first (+1) nucleosome serves as a strong transcrip-tional barrier in many eukaryotic genes ( 5 , 29 ).
In this case, RNAPII stalls owing to DNA-binding
factors or negative factors probably near the entry
of the nucleosome, and this paused complex differs
from that involved in gene-body transcription ( 30 ).
Further studies will clarify the mechanism of the
promoter-proximal regulation.Eharaet al.,Science 363 , 744–747 (2019) 15 February 2019 3of4
Fig. 2. The EC-nucleosome interactions at SHL(–1).(A) The EC-
nucleosome structures at SHL(–1) (red), SHL(–1)+1A(green), SHL(–1)+1B
(blue), and the RNAPII-nucleosome complex at SHL(–1) (PDB 6A5T; gray)
are superimposed in terms of RNAPII. The EC is colored as in Fig. 1.
(B) Close-up view of the EC-nucleosome interface at SHL(–1). RNAPII, Elf1,
and H3-H4 are overlaid with surface representations. The Rpb1 clamp
and the Rpb2 lobe are colored pale green and cyan, respectively. Spt4/5 is
omitted for clarity. (C) Elongation factor-induced bending of the
downstream DNA. The peeled DNA in the absence of elongation factors
(PDB 6A5V) is colored gray. The Elf1 N- and C-terminal tails are indicated
as dotted lines. (D) Close-up view of the Elf1-histone interface. The Zn2+
ion bound to Elf1 is shown as a gray sphere. (E) Elongation factor-induced
shift of the nucleosome. The nucleosomal DNA in the SHL(–1)+1B
complex is colored blue, and that in the absence of elongation factors
[SHL(–1)+1, PDB 6A5V] is colored orange. (F) The clamp head-nucleosome
interaction in the SHL(–1)+1Bcomplex. Elf1 is omitted for clarity.
(G) The same view as in (F) in the absence of elongation factors
(PDB 6A5V). (H) An assay analyzing the effect of the Elf1 N-terminal
tail on the nucleosomal transcription. The concentrations of Spt4/5
and Elf1 are 0.4 and 1.0mM, respectively.Fig. 3. The EC-nucleosome interactions at SHL(–5).(A) Close-up views
of the EC-nucleosome boundary at SHL(–5). Colors are as in Fig. 2B.
The EC and the nucleosomal DNA are overlaid with surface representa-
tions, showing a gap between them. (B) Elongation factor-induced bending
of the downstream DNA. The nucleosome in the SHL(–5) complex is
superimposed with that, without elongation factors (colored gray;
PDB 6A5P). (C) Elongation factor-induced shift of the nucleosome. The
SHL(–5) structure is superimposed with that, without elongation factors
(PDB 6A5P) in terms of RNAPII. The nucleosomal DNA in the latter
complex is colored gray.RESEARCH | REPORT
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