ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration

Jie Wang; Cristina Zibetti; Peng Shang; Srinivasa R. Sripathi; Pingwu Zhang; Marisol Cano; Thanh Hoang; Shuli Xia; Hongkai Ji; Shannath L. Merbs; Donald J. Zack; James T. Handa; Debasish Sinha; Seth Blackshaw; Jiang Qian

doi:10.1038/s41467-018-03856-y

ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration

Jie Wang, Cristina Zibetti, Peng Shang, Srinivasa R. Sripathi, Pingwu Zhang, Marisol Cano, Thanh Hoang, Shuli Xia, Hongkai Ji, Shannath L. Merbs, Donald J. Zack, James T. Handa, Debasish Sinha, Seth Blackshaw, Jiang Qian

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

39 Scopus citations

Abstract

Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.

Original language	English (US)
Article number	1364
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-03856-y
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Physics and Astronomy
General Chemistry
General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1038/s41467-018-03856-y

Cite this

Wang, J., Zibetti, C., Shang, P., Sripathi, S. R., Zhang, P., Cano, M., Hoang, T., Xia, S., Ji, H., Merbs, S. L., Zack, D. J., Handa, J. T., Sinha, D., Blackshaw, S., & Qian, J. (2018). ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration. Nature communications, 9(1), Article 1364. https://doi.org/10.1038/s41467-018-03856-y

@article{576711971150425d943b1ffe3f60add1,

title = "ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration",

abstract = "Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.",

author = "Jie Wang and Cristina Zibetti and Peng Shang and Sripathi, {Srinivasa R.} and Pingwu Zhang and Marisol Cano and Thanh Hoang and Shuli Xia and Hongkai Ji and Merbs, {Shannath L.} and Zack, {Donald J.} and Handa, {James T.} and Debasish Sinha and Seth Blackshaw and Jiang Qian",

note = "Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = dec,

day = "1",

doi = "10.1038/s41467-018-03856-y",

language = "English (US)",

volume = "9",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration

AU - Wang, Jie

AU - Zibetti, Cristina

AU - Shang, Peng

AU - Sripathi, Srinivasa R.

AU - Zhang, Pingwu

AU - Cano, Marisol

AU - Hoang, Thanh

AU - Xia, Shuli

AU - Ji, Hongkai

AU - Merbs, Shannath L.

AU - Zack, Donald J.

AU - Handa, James T.

AU - Sinha, Debasish

AU - Blackshaw, Seth

AU - Qian, Jiang

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.

AB - Age-related macular degeneration (AMD) is a significant cause of vision loss in the elderly. The extent to which epigenetic changes regulate AMD progression is unclear. Here we globally profile chromatin accessibility using ATAC-Seq in the retina and retinal pigmented epithelium (RPE) from AMD and control patients. Global decreases in chromatin accessibility occur in the RPE with early AMD, and in the retina of advanced disease, suggesting that dysfunction in the RPE drives disease onset. Footprints of photoreceptor and RPE-specific transcription factors are enriched in differentially accessible regions (DARs). Genes associated with DARs show altered expression in AMD. Cigarette smoke treatment of RPE cells recapitulates chromatin accessibility changes seen in AMD, providing an epigenetic link between a known risk factor for AMD and AMD pathology. Finally, overexpression of HDAC11 is partially responsible for the observed reduction in chromatin accessibility, suggesting that HDAC11 may be a potential new therapeutic target for AMD.

UR - http://www.scopus.com/inward/record.url?scp=85045282873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045282873&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-03856-y

DO - 10.1038/s41467-018-03856-y

M3 - Article

C2 - 29636475

AN - SCOPUS:85045282873

SN - 2041-1723

VL - 9

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 1364

ER -

ATAC-Seq analysis reveals a widespread decrease of chromatin accessibility in age-related macular degeneration

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this