Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment

Jillian M. Pattison; Sandra P. Melo; Samantha N. Piekos; Jessica L. Torkelson; Elizaveta Bashkirova; Maxwell R. Mumbach; Charlotte Rajasingh; Hanson Hui Zhen; Lingjie Li; Eric Liaw; Daniel Alber; Adam J. Rubin; Gautam Shankar; Xiaomin Bao; Howard Y. Chang; Paul A. Khavari; Anthony E. Oro

doi:10.1038/s41588-018-0263-0

Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment

Jillian M. Pattison, Sandra P. Melo, Samantha N. Piekos, Jessica L. Torkelson, Elizaveta Bashkirova, Maxwell R. Mumbach, Charlotte Rajasingh, Hanson Hui Zhen, Lingjie Li, Eric Liaw, Daniel Alber, Adam J. Rubin, Gautam Shankar, Xiaomin Bao, Howard Y. Chang, Paul A. Khavari, Anthony E. Oro^*

^*Corresponding author for this work

Molecular Biosciences

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

47 Scopus citations

Abstract

Human embryonic stem cell (hESC) differentiation promises advances in regenerative medicine ^1–3 , yet conversion of hESCs into transplantable cells or tissues remains poorly understood. Using our keratinocyte differentiation system, we employ a multi-dimensional genomics approach to interrogate the contributions of inductive morphogens retinoic acid and bone morphogenetic protein 4 (BMP4) and the epidermal master regulator p63 (encoded by TP63) ^4,5 during surface ectoderm commitment. In contrast to other master regulators ^6–9 , p63 effects major transcriptional changes only after morphogens alter chromatin accessibility, establishing an epigenetic landscape for p63 to modify. p63 distally closes chromatin accessibility and promotes accumulation of H3K27me3 (trimethylated histone H3 lysine 27). Cohesin HiChIP ¹⁰ visualizations of chromosome conformation show that p63 and the morphogens contribute to dynamic long-range chromatin interactions, as illustrated by TFAP2C regulation ¹¹ . Our study demonstrates the unexpected dependency of p63 on morphogenetic signaling and provides novel insights into how a master regulator can specify diverse transcriptional programs based on the chromatin landscape induced by exposure to specific morphogens.

Original language	English (US)
Pages (from-to)	1658-1665
Number of pages	8
Journal	Nature Genetics
Volume	50
Issue number	12
DOIs	https://doi.org/10.1038/s41588-018-0263-0
State	Published - Dec 1 2018

ASJC Scopus subject areas

Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41588-018-0263-0

Cite this

Pattison, J. M., Melo, S. P., Piekos, S. N., Torkelson, J. L., Bashkirova, E., Mumbach, M. R., Rajasingh, C., Zhen, H. H., Li, L., Liaw, E., Alber, D., Rubin, A. J., Shankar, G., Bao, X., Chang, H. Y., Khavari, P. A., & Oro, A. E. (2018). Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment. Nature Genetics, 50(12), 1658-1665. https://doi.org/10.1038/s41588-018-0263-0

@article{abb492937c21484e9f93c7a36038ce9e,

title = "Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment",

abstract = " Human embryonic stem cell (hESC) differentiation promises advances in regenerative medicine 1–3 , yet conversion of hESCs into transplantable cells or tissues remains poorly understood. Using our keratinocyte differentiation system, we employ a multi-dimensional genomics approach to interrogate the contributions of inductive morphogens retinoic acid and bone morphogenetic protein 4 (BMP4) and the epidermal master regulator p63 (encoded by TP63) 4,5 during surface ectoderm commitment. In contrast to other master regulators 6–9 , p63 effects major transcriptional changes only after morphogens alter chromatin accessibility, establishing an epigenetic landscape for p63 to modify. p63 distally closes chromatin accessibility and promotes accumulation of H3K27me3 (trimethylated histone H3 lysine 27). Cohesin HiChIP 10 visualizations of chromosome conformation show that p63 and the morphogens contribute to dynamic long-range chromatin interactions, as illustrated by TFAP2C regulation 11 . Our study demonstrates the unexpected dependency of p63 on morphogenetic signaling and provides novel insights into how a master regulator can specify diverse transcriptional programs based on the chromatin landscape induced by exposure to specific morphogens.",

author = "Pattison, {Jillian M.} and Melo, {Sandra P.} and Piekos, {Samantha N.} and Torkelson, {Jessica L.} and Elizaveta Bashkirova and Mumbach, {Maxwell R.} and Charlotte Rajasingh and Zhen, {Hanson Hui} and Lingjie Li and Eric Liaw and Daniel Alber and Rubin, {Adam J.} and Gautam Shankar and Xiaomin Bao and Chang, {Howard Y.} and Khavari, {Paul A.} and Oro, {Anthony E.}",

note = "Publisher Copyright: {\textcopyright} 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41588-018-0263-0",

language = "English (US)",

volume = "50",

pages = "1658--1665",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

}

Pattison, JM, Melo, SP, Piekos, SN, Torkelson, JL, Bashkirova, E, Mumbach, MR, Rajasingh, C, Zhen, HH, Li, L, Liaw, E, Alber, D, Rubin, AJ, Shankar, G, Bao, X, Chang, HY, Khavari, PA & Oro, AE 2018, 'Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment', Nature Genetics, vol. 50, no. 12, pp. 1658-1665. https://doi.org/10.1038/s41588-018-0263-0

TY - JOUR

T1 - Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment

AU - Pattison, Jillian M.

AU - Melo, Sandra P.

AU - Piekos, Samantha N.

AU - Torkelson, Jessica L.

AU - Bashkirova, Elizaveta

AU - Mumbach, Maxwell R.

AU - Rajasingh, Charlotte

AU - Zhen, Hanson Hui

AU - Li, Lingjie

AU - Liaw, Eric

AU - Alber, Daniel

AU - Rubin, Adam J.

AU - Shankar, Gautam

AU - Bao, Xiaomin

AU - Chang, Howard Y.

AU - Khavari, Paul A.

AU - Oro, Anthony E.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Human embryonic stem cell (hESC) differentiation promises advances in regenerative medicine 1–3 , yet conversion of hESCs into transplantable cells or tissues remains poorly understood. Using our keratinocyte differentiation system, we employ a multi-dimensional genomics approach to interrogate the contributions of inductive morphogens retinoic acid and bone morphogenetic protein 4 (BMP4) and the epidermal master regulator p63 (encoded by TP63) 4,5 during surface ectoderm commitment. In contrast to other master regulators 6–9 , p63 effects major transcriptional changes only after morphogens alter chromatin accessibility, establishing an epigenetic landscape for p63 to modify. p63 distally closes chromatin accessibility and promotes accumulation of H3K27me3 (trimethylated histone H3 lysine 27). Cohesin HiChIP 10 visualizations of chromosome conformation show that p63 and the morphogens contribute to dynamic long-range chromatin interactions, as illustrated by TFAP2C regulation 11 . Our study demonstrates the unexpected dependency of p63 on morphogenetic signaling and provides novel insights into how a master regulator can specify diverse transcriptional programs based on the chromatin landscape induced by exposure to specific morphogens.

AB - Human embryonic stem cell (hESC) differentiation promises advances in regenerative medicine 1–3 , yet conversion of hESCs into transplantable cells or tissues remains poorly understood. Using our keratinocyte differentiation system, we employ a multi-dimensional genomics approach to interrogate the contributions of inductive morphogens retinoic acid and bone morphogenetic protein 4 (BMP4) and the epidermal master regulator p63 (encoded by TP63) 4,5 during surface ectoderm commitment. In contrast to other master regulators 6–9 , p63 effects major transcriptional changes only after morphogens alter chromatin accessibility, establishing an epigenetic landscape for p63 to modify. p63 distally closes chromatin accessibility and promotes accumulation of H3K27me3 (trimethylated histone H3 lysine 27). Cohesin HiChIP 10 visualizations of chromosome conformation show that p63 and the morphogens contribute to dynamic long-range chromatin interactions, as illustrated by TFAP2C regulation 11 . Our study demonstrates the unexpected dependency of p63 on morphogenetic signaling and provides novel insights into how a master regulator can specify diverse transcriptional programs based on the chromatin landscape induced by exposure to specific morphogens.

UR - http://www.scopus.com/inward/record.url?scp=85056195213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056195213&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0263-0

DO - 10.1038/s41588-018-0263-0

M3 - Letter

C2 - 30397335

AN - SCOPUS:85056195213

SN - 1061-4036

VL - 50

SP - 1658

EP - 1665

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this