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Homo sapiens

ABSTRACT: Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

PROVIDER: PRJNA230632 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1043000.fastq.gz	Fastqsanger.gz
	SRR1043001.fastq.gz	Fastqsanger.gz
	SRR1043002.fastq.gz	Fastqsanger.gz
	SRR1043003.fastq.gz	Fastqsanger.gz
	SRR1042999.fastq.gz	Fastqsanger.gz

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Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

Project description:Lysine Specific Demethylase 1 (LSD1, KDM1A) functions as a transcriptional corepressor through demethylation of histone 3 lysine 4 (H3K4), but has coactivator function on some genes through unclear mechanisms. We show that LSD1, interacting with CoREST, associates with and coactivates androgen receptor (AR) on a large fraction of androgen-stimulated genes. A subset of these AR/LSD1-associated enhancer sites have histone 3 threonine 6 phosphorylation (H3T6ph), and these sites are further enriched for androgen-stimulated genes. Significantly, despite its coactivator activity, LSD1 still mediates H3K4me2 demethylation at these androgen-stimulated enhancers. FOXA1 is also associated with LSD1 at AR regulated enhancer sites, and a FOXA1 interaction with LSD1 enhances binding of both proteins at these sites. These findings show LSD1 functions broadly as a regulator of AR function, that it maintains a transcriptional repression function at AR-regulated enhancers through H3K4 demethylation, and has a distinct AR-linked coactivator function mediated by demethylation of other substrates. Determine the role of LSD1 in androgen signaling.

2014-12-12 | E-GEOD-52201 | biostudies-arrayexpress

Lysine-Specific Demethylase 1 Has Dual Functions as a Major Regulator of Androgen Receptor Transcriptional Activity

2014-12-12 | GSE52201 | GEO

The histone demethylase KDM3A regulates the transcriptional program of the androgen receptor in prostate cancer cells

Project description:The lysine demethylase 3A (KDM3A, JMJD1A or JHDM2A) controls transcriptional networks in a variety of biological processes such as spermatogenesis, metabolism, stem cell activity and tumor progression. We matched transcriptomic and ChIP-Seq profiles to decipher a genome-wide regulatory network of epigenetic control by KDM3A in prostate cancer cells. ChIP-Seq experiments monitoring histone 3 lysine 9 (H3K9) methylation marks show global histone demethylation effects of KDM3A. Combined assessment of histone demethylation events and gene expression changes presented major transcriptional activation suggesting that distinct oncogenic regulators may synergize with the epigenetic patterns by KDM3A. Pathway enrichment analysis of cells with KDM3A knockdown prioritized androgen signaling indicating that KDM3A plays a key role in regulating androgen receptor activity. Matched ChIP-Seq and knockdown experiments of KDM3A in combination with ChIP-Seq of the androgen receptor resulted in a gain of H3K9 methylation marks around androgen receptor binding sites of selected transcriptional targets in androgen signaling including positive regulation of KRT19, NKX3-1, KLK3, NDRG1, MAF, CREB3L4, MYC, INPP4B, PTK2B, MAPK1, MAP2K1, IGF1, E2F1, HSP90AA1, HIF1A, and ACSL3. The cancer systems biology analysis of KDM3A-dependent genes identifies an epigenetic and transcriptional network in androgen response, hypoxia, glycolysis, and lipid metabolism. Genome-wide ChIP-Seq data highlights specific gene targets and the ability of KDM3A to control oncogenic pathways in prostate cancer cells.

2019-05-15 | GSE109748 | GEO

Androgen Receptor Gene Expression in Prostate Cancer is Directly Suppressed by the Androgen Receptor Through Recruitment of Lysine Specific Demethylase 1

Project description:Androgen receptor (AR) is reactivated in castration resistant prostate cancer (CRPC) through mechanisms including marked increases in AR gene expression. We identify an enhancer in the AR second intron contributing to increased AR expression at low androgen levels in CRPC. Moreover, at increased androgen levels the AR binds this site and represses AR gene expression through recruitment of lysine specific demethylase 1 (LSD1) and H3K4me1,2 demethylation. AR similarly represses expression of multiple genes mediating androgen synthesis, DNA synthesis and proliferation, while stimulating genes mediating lipid and protein biosynthesis. Androgen levels in CRPC appear adequate to stimulate AR activity on enhancer elements, but not on suppressor elements, resulting in increased expression of AR and AR repressed genes that contribute to cellular proliferation. Custom Agilent 44K whole human genome expression oligonucleotide microarrays were used to profile pre-castrated androgen dependent, 4d-post-castrated, and relapsed castration resistant VCaP xenograft tumors in 3 mice. Total RNA was isolated and amplified prior to hybridization against a common reference pool of prostate tumor cell lines.

2011-08-15 | E-GEOD-31410 | biostudies-arrayexpress

Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells

Project description:Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells

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Homo sapiens

Project description:Androgen Receptor Gene Expression in Prostate Cancer is Directly Suppressed by the Androgen Receptor Through Recruitment of Lysine Specific Demethylase 1

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Androgen Receptor Gene Expression in Prostate Cancer is Directly Suppressed by the Androgen Receptor Through Recruitment of Lysine Specific Demethylase 1

2011-08-16 | GSE31410 | GEO

KDM4A regulated gene expression in human prostate cancer LNCaP cell

Project description:Histone lysine demethylase KDM4A is overexpressed in prostate cancer and plays a crucial role in tumor growth and survival. To understand the mechanisms underlying KDM4A-depedent cell growth and survival, microarray analysis was performed in LNCaP cells transduced with control or KDM4A specific-knockdown construct. The role of KDM4A in prostate carcinogenesis involves activation of E2F1 and androgen receptor transcriptional profiles. LNCaP cells were transduced by lentivirus carrying control pLKO.1 (empty vector) or shKDM4A construct (KDM4A-specific shRNA) for three days, followed by RNA extraction. Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays were used for microarray analysis.

2016-07-26 | E-GEOD-77928 | biostudies-arrayexpress

KDM4A regulated gene expression in human prostate cancer LNCaP cell

2016-07-26 | GSE77928 | GEO

Homo sapiens

Project description:Lysine-specific demethylase 1 metastasis of androgen-independent PCa cells [ChIP-seq]

| PRJNA245396 | ENA