H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

Hadas Hezroni; Itai Tzchori; Anna Davidi; Anna Mattout; Alva Biran; Malka Nissim-Rafinia; Heiner Westphal; Eran Meshorer

doi:10.4161/nucl.2.4.16767

H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

Hadas Hezroni, Itai Tzchori, Anna Davidi, Anna Mattout, Alva Biran, Malka Nissim-Rafinia, Heiner Westphal, Eran Meshorer^*

^*Corresponding author for this work

Department of Genetics

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

62 Scopus citations

Abstract

The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency.

Original language	English
Pages (from-to)	300-309
Number of pages	10
Journal	Nucleus
Volume	2
Issue number	4
DOIs	https://doi.org/10.4161/nucl.2.4.16767
State	Published - 2011

Bibliographical note

Funding Information:
The authors would like to thank Asher Meshorer for histopathological analyses and Evgenia Leikina for technical assistant with the fusion protocols and for helpful comments. This work was supported by funds from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH/HHS, the Israel Science Foundation (215/07 and 943/09) (to E.M.); the Israel Ministry of Health (6007) (to E.M.), the EU (IRG-206872 and 238176) (to E.M.), the ICRF (to A.M. and E.M.), The HUJI Internal Applicative Medical Grants (to E.M.), the Israeli Psychobiology Institute (to E.M.) and an Alon Fellowship (to E.M.). E.M. is a Joseph H. and Belle R. Braun Senior Lecturer in Life Sciences. H.H. is an Edmond J. Safra Fellow.

Keywords

Chromatin plasticity
Embryonic stem cells
Histone acetylation
Histone modifications

Access to Document

10.4161/nucl.2.4.16767

Cite this

@article{74e257f11bd540b68ff083e1a4d1beaf,

title = "H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells",

abstract = "The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency.",

keywords = "Chromatin plasticity, Embryonic stem cells, Histone acetylation, Histone modifications",

author = "Hadas Hezroni and Itai Tzchori and Anna Davidi and Anna Mattout and Alva Biran and Malka Nissim-Rafinia and Heiner Westphal and Eran Meshorer",

note = "Funding Information: The authors would like to thank Asher Meshorer for histopathological analyses and Evgenia Leikina for technical assistant with the fusion protocols and for helpful comments. This work was supported by funds from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH/HHS, the Israel Science Foundation (215/07 and 943/09) (to E.M.); the Israel Ministry of Health (6007) (to E.M.), the EU (IRG-206872 and 238176) (to E.M.), the ICRF (to A.M. and E.M.), The HUJI Internal Applicative Medical Grants (to E.M.), the Israeli Psychobiology Institute (to E.M.) and an Alon Fellowship (to E.M.). E.M. is a Joseph H. and Belle R. Braun Senior Lecturer in Life Sciences. H.H. is an Edmond J. Safra Fellow.",

year = "2011",

doi = "10.4161/nucl.2.4.16767",

language = "אנגלית",

volume = "2",

pages = "300--309",

journal = "Nucleus",

issn = "1949-1034",

publisher = "Landes Bioscience",

number = "4",

}

TY - JOUR

T1 - H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

AU - Hezroni, Hadas

AU - Tzchori, Itai

AU - Davidi, Anna

AU - Mattout, Anna

AU - Biran, Alva

AU - Nissim-Rafinia, Malka

AU - Westphal, Heiner

AU - Meshorer, Eran

N1 - Funding Information: The authors would like to thank Asher Meshorer for histopathological analyses and Evgenia Leikina for technical assistant with the fusion protocols and for helpful comments. This work was supported by funds from the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development/NIH/HHS, the Israel Science Foundation (215/07 and 943/09) (to E.M.); the Israel Ministry of Health (6007) (to E.M.), the EU (IRG-206872 and 238176) (to E.M.), the ICRF (to A.M. and E.M.), The HUJI Internal Applicative Medical Grants (to E.M.), the Israeli Psychobiology Institute (to E.M.) and an Alon Fellowship (to E.M.). E.M. is a Joseph H. and Belle R. Braun Senior Lecturer in Life Sciences. H.H. is an Edmond J. Safra Fellow.

PY - 2011

Y1 - 2011

N2 - The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency.

AB - The pluripotent genome is characterized by unique epigenetic features and a decondensed chromatin conformation. However, the relationship between epigenetic regulation and pluripotency is not altogether clear. Here, using an enhanced MEF/ESC fusion protocol, we compared the reprogramming potency and histone modifications of different embryonic stem cell (ESC) lines (R1, J1, E14, C57BL/6) and found that E14 ESCs are significantly less potent, with significantly reduced H3K9ac levels. Treatment of E14 ESCs with histone deacetylase (HDAC) inhibitors (HDACi) increased H3K9ac levels and restored their reprogramming capacity. Microarray and H3K9ac ChIP-seq analyses, suggested increased extracellular matrix (ECM) activity following HDACi treatment in E14 ESCs. These data suggest that H3K9ac may predict pluripotency and that increasing pluripotency by HDAC inhibition acts through H3K9ac to enhance the activity of target genes involved in ECM production to support pluripotency.

KW - Chromatin plasticity

KW - Embryonic stem cells

KW - Histone acetylation

KW - Histone modifications

UR - http://www.scopus.com/inward/record.url?scp=80053924587&partnerID=8YFLogxK

U2 - 10.4161/nucl.2.4.16767

DO - 10.4161/nucl.2.4.16767

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 21941115

AN - SCOPUS:80053924587

SN - 1949-1034

VL - 2

SP - 300

EP - 309

JO - Nucleus

JF - Nucleus

IS - 4

ER -

H3K9 histone acetylation predicts pluripotency and reprogramming capacity of ES cells

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this