TY - JOUR
T1 - A hyperdynamic H3.3 nucleosome marks promoter regions in pluripotent embryonic stem cells
AU - Schlesinger, Sharon
AU - Kaffe, Binyamin
AU - Melcer, Shai
AU - Aguilera, Jose D.
AU - Sivaraman, Divya M.
AU - Kaplan, Tommy
AU - Meshorer, Eran
N1 - Publisher Copyright:
C The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Histone variants and their chaperones are key regulators of eukaryotic transcription, and are critical for normal development. The histone variant H3.3 has been shown to play important roles in pluripotency and differentiation, and although its genome-wide patterns have been investigated, little is known about the role of its dynamic turnover in transcriptional regulation. To elucidate the role of H3.3 dynamics in embryonic stem cell (ESC) biology, we generated mouse ESC lines carrying a single copy of a doxycycline (Dox)-inducible HA-tagged version of H3.3 and monitored the rate of H3.3 incorporation by ChIP-seq at varying time points following Dox induction, before and after RA-induced differentiation. Comparing H3.3 turnover profiles in ESCs and RA-treated cells, we identified a hyperdynamic H3.3-containing nucleosome at the −1 position in promoters of genes expressed in ESCs. This dynamic nucleosome is restricted and shifted downstream into the +1 position following differentiation. We suggest that histone turnover dynamics provides an additional mechanism involved in expression regulation, and that a hyperdynamic −1 nucleosome marks promoters in ESCs. Our data provide evidence for regional regulation of H3.3 turnover in ESC promoters, and calls for testing, in high resolution, the dynamic behavior of additional histone variants and other structural chromatin proteins.
AB - Histone variants and their chaperones are key regulators of eukaryotic transcription, and are critical for normal development. The histone variant H3.3 has been shown to play important roles in pluripotency and differentiation, and although its genome-wide patterns have been investigated, little is known about the role of its dynamic turnover in transcriptional regulation. To elucidate the role of H3.3 dynamics in embryonic stem cell (ESC) biology, we generated mouse ESC lines carrying a single copy of a doxycycline (Dox)-inducible HA-tagged version of H3.3 and monitored the rate of H3.3 incorporation by ChIP-seq at varying time points following Dox induction, before and after RA-induced differentiation. Comparing H3.3 turnover profiles in ESCs and RA-treated cells, we identified a hyperdynamic H3.3-containing nucleosome at the −1 position in promoters of genes expressed in ESCs. This dynamic nucleosome is restricted and shifted downstream into the +1 position following differentiation. We suggest that histone turnover dynamics provides an additional mechanism involved in expression regulation, and that a hyperdynamic −1 nucleosome marks promoters in ESCs. Our data provide evidence for regional regulation of H3.3 turnover in ESC promoters, and calls for testing, in high resolution, the dynamic behavior of additional histone variants and other structural chromatin proteins.
UR - http://www.scopus.com/inward/record.url?scp=85039048106&partnerID=8YFLogxK
U2 - 10.1093/nar/gkx817
DO - 10.1093/nar/gkx817
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 29036702
AN - SCOPUS:85039048106
SN - 0305-1048
VL - 45
SP - 12181
EP - 12194
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 21
ER -