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Open Access Research article

Cell-specific occupancy of an extended repertoire of CREM and CREB binding loci in male germ cells

Igor Martianov1, Mohamed-Amin Choukrallah1, Arnaud Krebs1, Tao Ye1, Stephanie Legras1, Erikjan Rijkers2, Wilfred Van Ijcken2, Bernard Jost1, Paolo Sassone-Corsi3 and Irwin Davidson1*

Author Affiliations

1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UDS, 1 Rue Laurent Fries, 67404 Illkirch Cédex., France

2 Erasmus Medical Center, Dr Molewaterplein 50, 3015GE Rotterdam, the Netherlands

3 Department of Pharmacology, 2115 Gillespie Neuroscience, University of California, Irvine, California 92697-4625, USA

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BMC Genomics 2010, 11:530  doi:10.1186/1471-2164-11-530

Published: 29 September 2010

Abstract

Background

CREB and CREM are closely related factors that regulate transcription in response to various stress, metabolic and developmental signals. The CREMτ activator isoform is selectively expressed in haploid spermatids and plays an essential role in murine spermiogenesis.

Results

We have used chromatin immunoprecipitation coupled to sequencing (ChIP-seq) to map CREM and CREB target loci in round spermatids from adult mouse testis and spermatogonia derived GC1-spg cells respectively. We identify more than 9000 genomic loci most of which are cell-specifically occupied. Despite the fact that round spermatids correspond to a highly specialised differentiated state, our results show that they have a remarkably accessible chromatin environment as CREM occupies more than 6700 target loci corresponding not only to the promoters of genes selectively expressed in spermiogenesis, but also of genes involved in functions specific to other cell types. The expression of only a small subset of these target genes are affected in the round spermatids of CREM knockout animals. We also identify a set of intergenic binding loci some of which are associated with H3K4 trimethylation and elongating RNA polymerase II suggesting the existence of novel CREB and CREM regulated transcripts.

Conclusions

We demonstrate that CREM and CREB occupy a large number of promoters in highly cell specific manner. This is the first study of CREM target promoters directly in a physiologically relevant tissue in vivo and represents the most comprehensive experimental analysis of CREB/CREM regulatory potential to date.