Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming

Phuong Linh Bui; Ken Nishimura; Gonzalo Seminario Mondejar; Arun Kumar; Shiho Aizawa; Kensaku Murano; Kyosuke Nagata; Yohei Hayashi; Aya Fukuda; Yasuko Onuma; Yuzuru Ito; Mahito Nakanishi; Koji Hisatake

doi:10.1016/j.celrep.2019.10.010

Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming

Phuong Linh Bui, Ken Nishimura, Gonzalo Seminario Mondejar, Arun Kumar, Shiho Aizawa, Kensaku Murano, Kyosuke Nagata, Yohei Hayashi, Aya Fukuda, Yasuko Onuma, Yuzuru Ito, Mahito Nakanishi, Koji Hisatake

Department of Molecular Biology

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

Abstract

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by dramatic changes in epigenetic programs, including silencing of endogenous and exogenous retroviruses. Here, we utilized replication-defective and persistent Sendai virus (SeVdp)-based vectors to monitor retroviral silencing during reprogramming. We observed that retroviral silencing occurred at an early reprogramming stage without a requirement for KLF4 or the YY1-binding site in the retroviral genome. Insertional chromatin immunoprecipitation (iChIP) enabled us to isolate factors assembled on the silenced provirus, including components of inhibitor of histone acetyltransferase (INHAT), which includes the SET/TAF-I oncoprotein. Knockdown of SET/TAF-I in mouse embryonic fibroblasts (MEFs) diminished retroviral silencing during reprogramming, and overexpression of template activating factor-I α (TAF-Iα), a SET/TAF-I isoform predominant in embryonic stem cells (ESCs), reinforced retroviral silencing by an SeVdp-based vector that is otherwise defective in retroviral silencing. Our results indicate an important role for TAF-Iα in retroviral silencing during reprogramming.

Original language	English
Pages (from-to)	1909-1922.e5
Journal	Cell Reports
Volume	29
Issue number	7
DOIs	https://doi.org/10.1016/j.celrep.2019.10.010
Publication status	Published - 2019 Nov 12

Keywords

SeVdp vector
TAF-Iα
insertional chromatin immunoprecipitation
primer-binding site
reprogramming
retroviral silencing

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2019.10.010

Cite this

@article{0770f5d0794940e59026bf68ac00039c,

title = "Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming",

abstract = "Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by dramatic changes in epigenetic programs, including silencing of endogenous and exogenous retroviruses. Here, we utilized replication-defective and persistent Sendai virus (SeVdp)-based vectors to monitor retroviral silencing during reprogramming. We observed that retroviral silencing occurred at an early reprogramming stage without a requirement for KLF4 or the YY1-binding site in the retroviral genome. Insertional chromatin immunoprecipitation (iChIP) enabled us to isolate factors assembled on the silenced provirus, including components of inhibitor of histone acetyltransferase (INHAT), which includes the SET/TAF-I oncoprotein. Knockdown of SET/TAF-I in mouse embryonic fibroblasts (MEFs) diminished retroviral silencing during reprogramming, and overexpression of template activating factor-I α (TAF-Iα), a SET/TAF-I isoform predominant in embryonic stem cells (ESCs), reinforced retroviral silencing by an SeVdp-based vector that is otherwise defective in retroviral silencing. Our results indicate an important role for TAF-Iα in retroviral silencing during reprogramming.",

keywords = "SeVdp vector, TAF-Iα, insertional chromatin immunoprecipitation, primer-binding site, reprogramming, retroviral silencing",

author = "Bui, {Phuong Linh} and Ken Nishimura and {Seminario Mondejar}, Gonzalo and Arun Kumar and Shiho Aizawa and Kensaku Murano and Kyosuke Nagata and Yohei Hayashi and Aya Fukuda and Yasuko Onuma and Yuzuru Ito and Mahito Nakanishi and Koji Hisatake",

note = "Funding Information: This work was funded by JSPS KAKENHI grants JP16K07244 (K. Nishimura), JP19H03203 (K. Nishimura), JP19K22945 (K. Nishimura), JP19K07343 (A.F.), and JP17H04036 (K.H.). This study was also supported by the NIMS Molecule & Material Synthesis Platform “Nanotechnology Platform Project” operated by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. We are grateful to K. Kato for technical advice regarding TAF-I and T. Nishimura for technical assistance. Publisher Copyright: {\textcopyright} 2019 The Author(s)",

year = "2019",

month = nov,

day = "12",

doi = "10.1016/j.celrep.2019.10.010",

language = "English",

volume = "29",

pages = "1909--1922.e5",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "7",

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TY - JOUR

T1 - Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming

AU - Bui, Phuong Linh

AU - Nishimura, Ken

AU - Seminario Mondejar, Gonzalo

AU - Kumar, Arun

AU - Aizawa, Shiho

AU - Murano, Kensaku

AU - Nagata, Kyosuke

AU - Hayashi, Yohei

AU - Fukuda, Aya

AU - Onuma, Yasuko

AU - Ito, Yuzuru

AU - Nakanishi, Mahito

AU - Hisatake, Koji

N1 - Funding Information: This work was funded by JSPS KAKENHI grants JP16K07244 (K. Nishimura), JP19H03203 (K. Nishimura), JP19K22945 (K. Nishimura), JP19K07343 (A.F.), and JP17H04036 (K.H.). This study was also supported by the NIMS Molecule & Material Synthesis Platform “Nanotechnology Platform Project” operated by the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan. We are grateful to K. Kato for technical advice regarding TAF-I and T. Nishimura for technical assistance. Publisher Copyright: © 2019 The Author(s)

PY - 2019/11/12

Y1 - 2019/11/12

N2 - Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by dramatic changes in epigenetic programs, including silencing of endogenous and exogenous retroviruses. Here, we utilized replication-defective and persistent Sendai virus (SeVdp)-based vectors to monitor retroviral silencing during reprogramming. We observed that retroviral silencing occurred at an early reprogramming stage without a requirement for KLF4 or the YY1-binding site in the retroviral genome. Insertional chromatin immunoprecipitation (iChIP) enabled us to isolate factors assembled on the silenced provirus, including components of inhibitor of histone acetyltransferase (INHAT), which includes the SET/TAF-I oncoprotein. Knockdown of SET/TAF-I in mouse embryonic fibroblasts (MEFs) diminished retroviral silencing during reprogramming, and overexpression of template activating factor-I α (TAF-Iα), a SET/TAF-I isoform predominant in embryonic stem cells (ESCs), reinforced retroviral silencing by an SeVdp-based vector that is otherwise defective in retroviral silencing. Our results indicate an important role for TAF-Iα in retroviral silencing during reprogramming.

AB - Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) is accompanied by dramatic changes in epigenetic programs, including silencing of endogenous and exogenous retroviruses. Here, we utilized replication-defective and persistent Sendai virus (SeVdp)-based vectors to monitor retroviral silencing during reprogramming. We observed that retroviral silencing occurred at an early reprogramming stage without a requirement for KLF4 or the YY1-binding site in the retroviral genome. Insertional chromatin immunoprecipitation (iChIP) enabled us to isolate factors assembled on the silenced provirus, including components of inhibitor of histone acetyltransferase (INHAT), which includes the SET/TAF-I oncoprotein. Knockdown of SET/TAF-I in mouse embryonic fibroblasts (MEFs) diminished retroviral silencing during reprogramming, and overexpression of template activating factor-I α (TAF-Iα), a SET/TAF-I isoform predominant in embryonic stem cells (ESCs), reinforced retroviral silencing by an SeVdp-based vector that is otherwise defective in retroviral silencing. Our results indicate an important role for TAF-Iα in retroviral silencing during reprogramming.

KW - SeVdp vector

KW - TAF-Iα

KW - insertional chromatin immunoprecipitation

KW - primer-binding site

KW - reprogramming

KW - retroviral silencing

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U2 - 10.1016/j.celrep.2019.10.010

DO - 10.1016/j.celrep.2019.10.010

M3 - Article

C2 - 31722206

AN - SCOPUS:85074663537

SN - 2211-1247

VL - 29

SP - 1909-1922.e5

JO - Cell Reports

JF - Cell Reports

IS - 7

ER -

Template Activating Factor-I α Regulates Retroviral Silencing during Reprogramming

Abstract

Keywords

ASJC Scopus subject areas

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