TY - JOUR
T1 - MNase, as a probe to study the sequence-dependent site exposures in the +1 nucleosomes of yeast
AU - Luo, Di
AU - Kato, Daiki
AU - Nogami, Jumpei
AU - Ohkawa, Yasuyuki
AU - Kurumizaka, Hitoshi
AU - Kono, Hidetoshi
N1 - Funding Information:
Ministry of Education, Culture, Sports, Science and Technology (MEXT) Strategic Programs for Innovative Research, Computational Life Science and Application in Drug Discovery and Medical Development [hp160223, hp170255, hp18019 to H.Ko.]; Japan Society for the Promotion of Science KAKENHI [JP25116002, JP17H01408 to H.Ku., JP25116003 to H.Ko., JP251160010 to Y.O.]; Platform Project for Supporting in Drug Discovery and Life Science Research from the Japan Agency for Medical Research and Development (AMED) [JP18am0101076 to H.Ku., JP18am0101106 to H.Ko.]; Japan Science and Technology Agency CREST [JPMJCR16G1 to Y.O.]. Funding for open access charge: Ministry of Education, Culture, Sports, Science and Technology (MEXT) Strategic Programs for Innovative Research, Computational Life Science and Application in Drug Discovery and Medical Development [hp180191 to H. Ko.]. Conflict of interest statement. None declared.
Publisher Copyright:
© The Author(s) 2018.
PY - 2018/8/21
Y1 - 2018/8/21
N2 - The first nucleosomes in the downstream of transcription starting sites are called +1 nucleosomes, which are expected to be readily unwrapped for DNA transcription. To investigate DNA accessibility in +1 nucleosomes, MNase-seq experiments were carried out with 20 reconstituted +1 nucleosomes of budding yeast. Although MNase has been known for its sequence preference in DNA digestions, we confirmed that this sequence preference is overwhelmed by DNA accessibility by identifying the sequence-driven and accessibility-driven cleavages. Specifically, we find that sequences favoured by MNase at the end regions such as TA dinucleotide are prohibited from cleavage at the internal sites in the early stage of digestion. Nevertheless, sequences less favoured by MNase at the end regions such as AA/TT dinucleotide are predominantly cleaved at the internal sites in the early stage of digestion. Since AA/TT is known as a rigid dinucleotide step resistant to DNA bending, these internal cleavages reflect the local site exposures induced by DNA mechanics. As the DNA entry site of +1 nucleosomes in yeast is found AA/TT-rich, this sequence element may play a role in gene activation by reducing DNA-histone affinities along the direction of DNA transcription.
AB - The first nucleosomes in the downstream of transcription starting sites are called +1 nucleosomes, which are expected to be readily unwrapped for DNA transcription. To investigate DNA accessibility in +1 nucleosomes, MNase-seq experiments were carried out with 20 reconstituted +1 nucleosomes of budding yeast. Although MNase has been known for its sequence preference in DNA digestions, we confirmed that this sequence preference is overwhelmed by DNA accessibility by identifying the sequence-driven and accessibility-driven cleavages. Specifically, we find that sequences favoured by MNase at the end regions such as TA dinucleotide are prohibited from cleavage at the internal sites in the early stage of digestion. Nevertheless, sequences less favoured by MNase at the end regions such as AA/TT dinucleotide are predominantly cleaved at the internal sites in the early stage of digestion. Since AA/TT is known as a rigid dinucleotide step resistant to DNA bending, these internal cleavages reflect the local site exposures induced by DNA mechanics. As the DNA entry site of +1 nucleosomes in yeast is found AA/TT-rich, this sequence element may play a role in gene activation by reducing DNA-histone affinities along the direction of DNA transcription.
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U2 - 10.1093/nar/gky502
DO - 10.1093/nar/gky502
M3 - Article
C2 - 29893974
AN - SCOPUS:85055042541
VL - 46
SP - 7124
EP - 7137
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 14
ER -