Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

Petko Fiziev; Kadir C. Akdemir; John P. Miller; Emily Z. Keung; Neha S. Samant; Sneha Sharma; Christopher A. Natale; Christopher J. Terranova; Mayinuer Maitituoheti; Samirkumar B. Amin; Emmanuel Martinez-Ledesma; Mayura Dhamdhere; Jacob B. Axelrad; Amiksha Shah; Christine S. Cheng; Harshad Mahadeshwar; Sahil Seth; Michelle C. Barton; Alexei Protopopov; Kenneth Y. Tsai; Michael A. Davies; Benjamin A. Garcia; Ido Amit; Lynda Chin; Jason Ernst; Kunal Rai

doi:10.1016/j.celrep.2017.03.078

Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

Petko Fiziev, Kadir C. Akdemir, John P. Miller, Emily Z. Keung, Neha S. Samant, Sneha Sharma, Christopher A. Natale, Christopher J. Terranova, Mayinuer Maitituoheti, Samirkumar B. Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B. Axelrad, Amiksha Shah, Christine S. Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C. Barton, Alexei Protopopov, Kenneth Y. TsaiMichael A. Davies, Benjamin A. Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai

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

56 Scopus citations

Abstract

The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.

Original language	English (US)
Pages (from-to)	875-889
Number of pages	15
Journal	Cell Reports
Volume	19
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2017.03.078
State	Published - Apr 25 2017
Externally published	Yes

Keywords

CBP
ChIP-seq
DUSP5
HDAC
chromatin state
epigenome
histone modifications
melanoma

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2017.03.078

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Fiziev, P., Akdemir, K. C., Miller, J. P., Keung, E. Z., Samant, N. S., Sharma, S., Natale, C. A., Terranova, C. J., Maitituoheti, M., Amin, S. B., Martinez-Ledesma, E., Dhamdhere, M., Axelrad, J. B., Shah, A., Cheng, C. S., Mahadeshwar, H., Seth, S., Barton, M. C., Protopopov, A., ... Rai, K. (2017). Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression. Cell Reports, 19(4), 875-889. https://doi.org/10.1016/j.celrep.2017.03.078

Fiziev, P, Akdemir, KC, Miller, JP, Keung, EZ, Samant, NS, Sharma, S, Natale, CA, Terranova, CJ, Maitituoheti, M, Amin, SB, Martinez-Ledesma, E, Dhamdhere, M, Axelrad, JB, Shah, A, Cheng, CS, Mahadeshwar, H, Seth, S, Barton, MC, Protopopov, A, Tsai, KY, Davies, MA, Garcia, BA, Amit, I, Chin, L, Ernst, J & Rai, K 2017, 'Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression', Cell Reports, vol. 19, no. 4, pp. 875-889. https://doi.org/10.1016/j.celrep.2017.03.078

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title = "Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression",

abstract = "The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.",

keywords = "CBP, ChIP-seq, DUSP5, HDAC, chromatin state, epigenome, histone modifications, melanoma",

author = "Petko Fiziev and Akdemir, {Kadir C.} and Miller, {John P.} and Keung, {Emily Z.} and Samant, {Neha S.} and Sneha Sharma and Natale, {Christopher A.} and Terranova, {Christopher J.} and Mayinuer Maitituoheti and Amin, {Samirkumar B.} and Emmanuel Martinez-Ledesma and Mayura Dhamdhere and Axelrad, {Jacob B.} and Amiksha Shah and Cheng, {Christine S.} and Harshad Mahadeshwar and Sahil Seth and Barton, {Michelle C.} and Alexei Protopopov and Tsai, {Kenneth Y.} and Davies, {Michael A.} and Garcia, {Benjamin A.} and Ido Amit and Lynda Chin and Jason Ernst and Kunal Rai",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s)",

year = "2017",

month = apr,

day = "25",

doi = "10.1016/j.celrep.2017.03.078",

language = "English (US)",

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T1 - Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

AU - Fiziev, Petko

AU - Akdemir, Kadir C.

AU - Miller, John P.

AU - Keung, Emily Z.

AU - Samant, Neha S.

AU - Sharma, Sneha

AU - Natale, Christopher A.

AU - Terranova, Christopher J.

AU - Maitituoheti, Mayinuer

AU - Amin, Samirkumar B.

AU - Martinez-Ledesma, Emmanuel

AU - Dhamdhere, Mayura

AU - Axelrad, Jacob B.

AU - Shah, Amiksha

AU - Cheng, Christine S.

AU - Mahadeshwar, Harshad

AU - Seth, Sahil

AU - Barton, Michelle C.

AU - Protopopov, Alexei

AU - Tsai, Kenneth Y.

AU - Davies, Michael A.

AU - Garcia, Benjamin A.

AU - Amit, Ido

AU - Chin, Lynda

AU - Ernst, Jason

AU - Rai, Kunal

PY - 2017/4/25

Y1 - 2017/4/25

N2 - The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.

AB - The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways. Importantly, such acetylation changes were also observed between benign nevi and malignant melanoma human tissues. Intriguingly, only a small fraction of chromatin state transitions correlated with expected changes in gene expression patterns. Restoration of acetylation levels on deacetylated loci by histone deacetylase (HDAC) inhibitors selectively blocked excessive proliferation in tumorigenic cells and human melanoma cells, suggesting functional roles of observed chromatin state transitions in driving hyperproliferative phenotype. Through these results, we define functionally relevant chromatin states associated with melanoma progression.

KW - CBP

KW - ChIP-seq

KW - DUSP5

KW - HDAC

KW - chromatin state

KW - epigenome

KW - histone modifications

KW - melanoma

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AN - SCOPUS:85018668669

SN - 2211-1247

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SP - 875

EP - 889

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

Systematic Epigenomic Analysis Reveals Chromatin States Associated with Melanoma Progression

Abstract

Keywords

ASJC Scopus subject areas

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