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Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage

ABSTRACT: Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage

PROVIDER: PRJNA707430 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13884506_1.fastq.gz	Fastqsanger.gz
	SRR13884506_2.fastq.gz	Fastqsanger.gz
	SRR13884507_1.fastq.gz	Fastqsanger.gz
	SRR13884507_2.fastq.gz	Fastqsanger.gz
	SRR13884508_1.fastq.gz	Fastqsanger.gz

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Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage

Project description:Long noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting in early development. There has been rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences of these rare deeply conserved lncRNAs are typically not similar to each other. Here, we characterize HOXA-AS3 and HOXB-AS3, lncRNAs produced from the central regions of the HOXA and HOXB clusters. Sequence-similar orthologs of both lncRNAs are found in multiple vertebrate species and there is evident sequence similarity between their promoters, suggesting that the production of these lncRNAs predates the duplication of the HOX clusters at the root of the vertebrate lineage. This conservation extends to similar expression patterns of the two lncRNAs, in particular in cells transiently arising during early development or in the adult colon. Functionally, the RNA products of HOXA-AS3 and HOXB-AS3 regulate the expression of their overlapping HOX5–7 genes both in HT-29 cells and during differentiation of human embryonic stem cells. Beyond production of paralogous protein-coding and microRNA genes, the regulatory program in the HOX clusters therefore also relies on paralogous lncRNAs acting in restricted spatial and temporal windows of embryonic development and cell differentiation.

2021-03-09 | GSE168444 | GEO

Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage.

Project description:Long noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting in early development. There has been rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences of these rare deeply conserved lncRNAs are typically not similar to each other. Here, we characterize HOXA-AS3 and HOXB-AS3, lncRNAs produced from the central regions of the HOXA and HOXB clusters. Sequence-similar orthologs of both lncRNAs are found in multiple vertebrate species and there is evident sequence similarity between their promoters, suggesting that the production of these lncRNAs predates the duplication of the HOX clusters at the root of the vertebrate lineage. This conservation extends to similar expression patterns of the two lncRNAs, in particular in cells transiently arising during early development or in the adult colon. Functionally, the RNA products of HOXA-AS3 and HOXB-AS3 regulate the expression of their overlapping HOX5-7 genes both in HT-29 cells and during differentiation of human embryonic stem cells. Beyond production of paralogous protein-coding and microRNA genes, the regulatory program in the HOX clusters therefore also relies on paralogous lncRNAs acting in restricted spatial and temporal windows of embryonic development and cell differentiation.

| S-EPMC8330917 | biostudies-literature

Transcription profiling of normal and cancerous human breast cell lines and tissues to explore HOXA gene expression in context of other homological genes and in context of physical location in genome

Project description:Expression profiles of normal and cancerous cell and tissue were used for exploring HOXA genes expression in context of other homological genes (HOXB,HOXC,HOXD) and in context of physical location in genome

2006-11-03 | E-MEXP-882 | biostudies-arrayexpress

HOXB-AS3 expressions promote cell proliferation

Project description:We knock down HOXB-AS3 with shRNA in OCI/AML3 cell line to investigate the downstream pathways of HOXB-AS3 in the cell proliferation.

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The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

Project description:In this work we dissect the functional role of the HOXB-AS3 long non coding RNA in patients with NPM1-mutated (NPM1mut) acute myeloid leukemia (AML). We show that HOXB-AS3 regulates the proliferative capacity of NPM1mut AML blasts in vitro and in vivo. HOXB-AS3 was found to interact with the ErbB3-binding protein 1 (EBP1) and guide EBP1 to the ribosomal DNA locus. Via this mechanism HOXB-AS3 regulates ribosomal RNA transcription and de novo protein synthesis. We propose that in the context of NPM1 mutations, HOXB-AS3 overexpression acts as a compensatory mechanism, which allows adequate protein production in leukemic blasts.

2019-10-16 | PXD015520 | Pride

An enhancer cluster promotes NPCs formation from ESCs through maintaining HoxB activation by long-range chromatin interaction

Project description:Homeobox B cluster genes (HoxB) are important marker genes for neural progenitor cells (NPCs) formation from embryonic stem cells (ESCs). However, mechanisms of HoxB activation in NPCs remain largely unknown. Here, we find an enhancer cluster (EnC) interacting with the HoxB locus by PLAC-seq analysis. CRISPR/Cas9-mediated EnC deletion significantly inhibited HoxB expression, indicating that the EnC is required for HoxB activation in NPCs. Transcriptome analysis revealed that differentiation-related master control genes and NPCs formation-related signaling pathways were significantly inhibited suggesting that the EnC is essential for NPCs formation. In summary, our results reveal a new mechanism about HoxB activation depending on EnC is crucial for NPCs formation.

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The long non-coding RNA HOXB-AS3 regulates ribosomal RNA transcription in NPM1-mutated acute myeloid leukemia

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Two enhancers synergistically regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure

Project description:Homeobox B cluster (HoxB) genes play important roles in RA-induced early ESCs differentiation. In this study, we identified two enhancers synergistically regulate HoxB genes expressions through 3D chromatin structure and thus regulate RA-induced early ESCs differentiation. 4C data showed interactions between HoxB genes and the two enhancers. CRISPR/Cas9-mediated individual or compound deletion of the two enhancers significantly inhibits HoxB genes expressions while transcriptome analysis revealed that RA induced early ESCs differentiation was blocked in the enhancer KO cells. Our study suggests new mechanism by which two enhancers regulate HoxB genes expressions and retinoic acid-induced early ESCs differentiation through 3D chromatin structure.

2021-03-01 | GSE165725 | GEO

HOXB-AS3 expressions promote cell proliferation

Project description:HOXB-AS3 expressions promote cell proliferation

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Deletion of the Hoxa Cluster in MLL-AF9 Is Incompatible with Leukemia Maintenance: RNAseq-based Quantitative Analysis of Wild Type and Hoxa-del Transcriptomes

Project description:High HOXA expression correlates with poor clinical outcome in AML, particularly those harboring MLL rearrangements (MLLr). The necessity of the HOXA cluster for the maintenance of MLLr-leukemia has not been elucidated. Primary leukemias were generated by transduction of MLL-AF9 (MA9) into hematopoietic stem and progenitor cells from compound Cre responsive transgenic mice for conditional deletion of the Hoxa locus. Hoxa deletion resulted in reduced proliferation, colony formation and repopulating ability in transplanted mice in which surviving leukemic cells retained at least one copy of the Hoxa cluster (Hoxa-del). Comparative RNA-seq analysis of leukemic MA9-Hoxa-wild type (WT) and MA9-Hoxa-del cells identified a unique gene signature.

2021-04-16 | GSE113200 | GEO

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