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Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer

ABSTRACT: Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer

PROVIDER: PRJNA867703 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20993320.fastq.gz	Fastqsanger.gz
	SRR20993321.fastq.gz	Fastqsanger.gz
	SRR20993322.fastq.gz	Fastqsanger.gz
	SRR20993323.fastq.gz	Fastqsanger.gz
	SRR20993324.fastq.gz	Fastqsanger.gz

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Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (ATAC-Seq)

Project description:Neuroendocrine-like differentiation of castration-resistant prostate cancer is highly aggressive and independent of the androgen receptor signaling for its progression. During such lineage differentiation, adenocarcinoma adopts basal and neuronal characteristics that alter its clinical progression, limiting its therapeutic opportunities. Inadequate understanding of the molecular mechanism for such transformation also restricts its targeted therapies. Using ATAC-Seq, acetylated-histone ChIP-seq, and RNA-seq, we have characterized the early transformation process and identified chromatin occupancy and gene expression differences between adenocarcinoma and neuroendocrine-like cancer cells. By comparing differentially active promoter signatures during lineage-specific transcriptional events, our results indicate that the transcription factor Pax5 plays a major role in the trans-differentiation processes. Using LuCaP PDX tissues and metastatic prostate cancer TMA, in conjunction with patient RNA-expression databases, we validated that Pax5 is selectively expressed only in neuroendocrine like cancer but not in adenocarcinoma. Further analysis reveals that Pax5 expression is involved in neuronal gene expression and critical for imparting therapy resistance. Further, our results indicate that increased hydroxymethylation at the Pax5 promoter leads to recruitment of the homeobox transcription factor Pbx1 for Pax5 transcription. This is in line with our findings that lineage-specific expression of Pbx1/Pax5 is associated with the development of neuroendocrine-like differentiation. Our study suggests, upon continuous exposure to anti-androgen therapeutic stress, chromatin modifications are associated with Pax5-mediated gene expression to adopt neuroendocrine-like characteristics of advanced prostate cancer.

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Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (ChIP-Seq)

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Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (RNA-Seq)

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Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (RNA-Seq)

Project description:Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (RNA-Seq)

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Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (ATAC-Seq)

Project description:Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (ATAC-Seq)

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Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (ChIP-Seq)

Project description:Lineage specific chromatin modification guides Pax5 mediated gene expression in neuroendocrine like differentiation of prostate cancer (ChIP-Seq)

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PAX5 promotes heterocharomatin formation

Project description:Heterochromatin has a high density of DNA and low rates of gene transcription.H3k9me3 is a conserved histone modification, and is best known for its role in constitutive heterochromatin formation.H1155, which is a neuroendocrine large cell lung cancer cell line, has a dense nucleus and a high level of occupancy of H3K9me3. PAX5 is a neurogenesis and B lymphocyte development transcription factor, and endogenous expressed in neuroendocrine carcinoma, including H1155 cell line. To assess whether PAX5 promotes heterochromatin formation in H1155, we knock out PAX5 in H1155 cell (KO-PAX5) by CRISPR/Cas9 and use H3K9me3 to performed ChIP-seq.

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PAX5 promotes progression of neuroendocrine prostate cancer

Project description:Analysis of prostate adnocarcinoma cell line LNCaP cells overexpression pair box 5 (PAX5) for up to 4 days. The goals of this study are to compare PAX5 overexpression in LNCaP cell drives transcriptome profiling (RNA-seq) changes.

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