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HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma
by
Markus V. Heppt
, Alexander Matthies
, Robert Besch
, Claudia Kammerbauer
, Carola Berking
, Anja Wessely
, Silke Kuphal
, Melanie Kappelmann-Fenzl
, Lars E. French
, Saskia A. Graf
, Anja K. Bosserhoff
, Eva Hornig
in
Apoptosis
/ Cell cycle
/ Cell Line
/ DNA Methylation
/ Epigenesis, Genetic
/ Epigenetics
/ Ewings sarcoma
/ Fibroblasts
/ Gene expression
/ Gene Expression Regulation
/ Gene Expression Regulation - drug effects
/ Gene Silencing
/ Histone Deacetylase 2
/ Histone Deacetylase 2 - genetics
/ Histone Deacetylase 2 - metabolism
/ Histone Deacetylase Inhibitors
/ Histone Deacetylase Inhibitors - pharmacology
/ Humans
/ Melanocytes
/ Melanocytes - metabolism
/ Melanocytes - pathology
/ Melanoma
/ Melanoma - etiology
/ Melanoma - metabolism
/ Melanoma - pathology
/ melanoma; epigenetic regulation; BRN3A; HDAC; HAT; DNA methylation; ChIP-Seq
/ Nervous system
/ Protein expression
/ Proteins
/ Skin cancer
/ Transcription Factor Brn-3A
/ Transcription Factor Brn-3A - genetics
/ Transcription Factor Brn-3A - metabolism
/ Transcription factors
2022
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HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma
by
Markus V. Heppt
, Alexander Matthies
, Robert Besch
, Claudia Kammerbauer
, Carola Berking
, Anja Wessely
, Silke Kuphal
, Melanie Kappelmann-Fenzl
, Lars E. French
, Saskia A. Graf
, Anja K. Bosserhoff
, Eva Hornig
in
Apoptosis
/ Cell cycle
/ Cell Line
/ DNA Methylation
/ Epigenesis, Genetic
/ Epigenetics
/ Ewings sarcoma
/ Fibroblasts
/ Gene expression
/ Gene Expression Regulation
/ Gene Expression Regulation - drug effects
/ Gene Silencing
/ Histone Deacetylase 2
/ Histone Deacetylase 2 - genetics
/ Histone Deacetylase 2 - metabolism
/ Histone Deacetylase Inhibitors
/ Histone Deacetylase Inhibitors - pharmacology
/ Humans
/ Melanocytes
/ Melanocytes - metabolism
/ Melanocytes - pathology
/ Melanoma
/ Melanoma - etiology
/ Melanoma - metabolism
/ Melanoma - pathology
/ melanoma; epigenetic regulation; BRN3A; HDAC; HAT; DNA methylation; ChIP-Seq
/ Nervous system
/ Protein expression
/ Proteins
/ Skin cancer
/ Transcription Factor Brn-3A
/ Transcription Factor Brn-3A - genetics
/ Transcription Factor Brn-3A - metabolism
/ Transcription factors
2022
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HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma
by
Markus V. Heppt
, Alexander Matthies
, Robert Besch
, Claudia Kammerbauer
, Carola Berking
, Anja Wessely
, Silke Kuphal
, Melanie Kappelmann-Fenzl
, Lars E. French
, Saskia A. Graf
, Anja K. Bosserhoff
, Eva Hornig
in
Apoptosis
/ Cell cycle
/ Cell Line
/ DNA Methylation
/ Epigenesis, Genetic
/ Epigenetics
/ Ewings sarcoma
/ Fibroblasts
/ Gene expression
/ Gene Expression Regulation
/ Gene Expression Regulation - drug effects
/ Gene Silencing
/ Histone Deacetylase 2
/ Histone Deacetylase 2 - genetics
/ Histone Deacetylase 2 - metabolism
/ Histone Deacetylase Inhibitors
/ Histone Deacetylase Inhibitors - pharmacology
/ Humans
/ Melanocytes
/ Melanocytes - metabolism
/ Melanocytes - pathology
/ Melanoma
/ Melanoma - etiology
/ Melanoma - metabolism
/ Melanoma - pathology
/ melanoma; epigenetic regulation; BRN3A; HDAC; HAT; DNA methylation; ChIP-Seq
/ Nervous system
/ Protein expression
/ Proteins
/ Skin cancer
/ Transcription Factor Brn-3A
/ Transcription Factor Brn-3A - genetics
/ Transcription Factor Brn-3A - metabolism
/ Transcription factors
2022
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HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma
Journal Article
HDAC2 Is Involved in the Regulation of BRN3A in Melanocytes and Melanoma
2022
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Overview
The neural crest transcription factor BRN3A is essential for the proliferation and survival of melanoma cells. It is frequently expressed in melanoma but not in normal melanocytes or benign nevi. The mechanisms underlying the aberrant expression of BRN3A are unknown. Here, we investigated the epigenetic regulation of BRN3A in melanocytes and melanoma cell lines treated with DNA methyltransferase (DNMT), histone acetyltransferase (HAT), and histone deacetylase (HDAC) inhibitors. DNMT and HAT inhibition did not significantly alter BRN3A expression levels, whereas panHDAC inhibition by trichostatin A led to increased expression. Treatment with the isoform-specific HDAC inhibitor mocetinostat, but not with PCI-34051, also increased BRN3A expression levels, suggesting that class I HDACs HDAC1, HDAC2, and HDAC3, and class IV HDAC11, were involved in the regulation of BRN3A expression. Transient silencing of HDACs 1, 2, 3, and 11 by siRNAs revealed that, specifically, HDAC2 inhibition was able to increase BRN3A expression. ChIP-Seq analysis uncovered that HDAC2 inhibition specifically increased H3K27ac levels at a distal enhancer region of the BRN3A gene. Altogether, our data suggest that HDAC2 is a key epigenetic regulator of BRN3A in melanocytes and melanoma cells. These results highlight the importance of epigenetic mechanisms in regulating melanoma oncogenes.
Publisher
MDPI AG,MDPI
Subject
/ Gene Expression Regulation - drug effects
/ Histone Deacetylase 2 - genetics
/ Histone Deacetylase 2 - metabolism
/ Histone Deacetylase Inhibitors
/ Histone Deacetylase Inhibitors - pharmacology
/ Humans
/ Melanoma
/ melanoma; epigenetic regulation; BRN3A; HDAC; HAT; DNA methylation; ChIP-Seq
/ Proteins
/ Transcription Factor Brn-3A - genetics
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