Genome wide chromatin occupancy of mrhl RNA and its role in gene regulation in mouse spermatogonial cells

Akhade, V. S., Arun, G., Donakonda, S., Satyanarayana Rao, M. R. (2014) Genome wide chromatin occupancy of mrhl RNA and its role in gene regulation in mouse spermatogonial cells. RNA Biol, 11 (10). pp. 1262-79. ISSN 1547-6286

URL: http://www.ncbi.nlm.nih.gov/pubmed/25584904
DOI: 10.1080/15476286.2014.996070

Abstract

Mrhl RNA is a nuclear lncRNA encoded in the mouse genome and negatively regulates Wnt signaling in spermatogonial cells through p68/Ddx5 RNA helicase. Mrhl RNA is present in the chromatin fraction of mouse spermatogonial Gc1-Spg cells and genome wide chromatin occupancy of mrhl RNA by ChOP (Chromatin oligo affinity precipitation) technique identified 1370 statistically significant genomic loci. Among these, genes at 37 genomic loci also showed altered expression pattern upon mrhl RNA down regulation which are referred to as GRPAM (Genes Regulated by Physical Association of Mrhl RNA). p68 interacted with mrhl RNA in chromatin at these GRPAM loci. p68 silencing drastically reduced mrhl RNA occupancy at 27 GRPAM loci and also perturbed the expression of GRPAM suggesting a role for p68 mediated mrhl RNA occupancy in regulating GRPAM expression. Wnt3a ligand treatment of Gc1-Spg cells down regulated mrhl RNA expression and also perturbed expression of these 27 GRPAM genes that included genes regulating Wnt signaling pathway and spermatogenesis, one of them being Sox8, a developmentally important transcription factor. We also identified interacting proteins of mrhl RNA associated chromatin fraction which included Pc4, a chromatin organizer protein and hnRNP A/B and hnRNP A2/B1 which have been shown to be associated with lincRNA-Cox2 function in gene regulation. Our findings in the Gc1-Spg cell line also correlate with the results from analysis of mouse testicular tissue which further highlights the in vivo physiological significance of mrhl RNA in the context of gene regulation during mammalian spermatogenesis.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
CSHL Authors:
Communities: CSHL labs > Spector lab
Depositing User: Matt Covey
Date Deposited: 17 Feb 2015 19:26
Last Modified: 17 Feb 2015 19:26
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31216

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