Gene density profile reveals the marking of late replicated domains in the Drosophila melanogaster genome

Regulation of replication timing has been a focus of many studies. It has been shown that numerous chromosomal regions switch their replication timing on cell differentiation in Drosophila and mice. However, it is not clear which features of these regions are essential for such regulation. In this study, we examined the organization of late underreplicated regions (URs) of the Drosophila melanogaster genome. When compared with their flanks, these regions showed decreased gene density. A detailed view revealed that these regions originate from unusual combination of short genes and long intergenic spacers. Furthermore, gene expression study showed that this pattern is mostly contributed by short testis-specific genes abundant in the URs. Based on these observations, we developed a genome scanning algorithm and identified 110 regions possessing similar gene density and transcriptional profiles. According to the published data, replication of these regions has been significantly shifted towards late S-phase in two Drosophila cell lines and in polytene chromosomes. Our results suggest that genomic organization of the underreplicated areas of Drosophila polytene chromosomes may be associated with the regulation of their replication timing.

[1]  David M MacAlpine,et al.  Coordination of replication and transcription along a Drosophila chromosome. , 2004, Genes & development.

[2]  Dirk Schübeler,et al.  Global Reorganization of Replication Domains During Embryonic Stem Cell Differentiation , 2008, PLoS biology.

[3]  Alain Arneodo,et al.  Human gene organization driven by the coordination of replication and transcription. , 2007, Genome research.

[4]  M. Groudine,et al.  Long-Distance Control of Origin Choice and Replication Timing in the Human β-Globin Locus Are Independent of the Locus Control Region , 2000, Molecular and Cellular Biology.

[5]  B. van Steensel,et al.  SUUR joins separate subsets of PcG, HP1 and B-type lamin targets in Drosophila , 2007, Journal of Cell Science.

[6]  E. N. Andreyeva,et al.  Influence of the SuUR gene on intercalary heterochromatin in Drosophila melanogaster polytene chromosomes , 2002, Chromosoma.

[7]  Edward J Oakeley,et al.  Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome. , 2009, Genes & development.

[8]  Yuri Y. Shevelyov,et al.  Large clusters of co-expressed genes in the Drosophila genome , 2002, Nature.

[9]  I. Zhimulev.  Polytene chromosomes, heterochromatin, and position effect variegation. , 1998, Advances in genetics.

[10]  Ronald Berezney,et al.  Spatial and Temporal Dynamics of DNA Replication Sites in Mammalian Cells , 1998, The Journal of cell biology.

[11]  E. Salmon.  Gene Expression During the Life Cycle of Drosophila melanogaster , 2002 .

[12]  P. Spierer,et al.  The bithorax complex of Drosophila melanogaster: Underreplication and morphology in polytene chromosomes. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[13]  I. Zhimulev,et al.  Intercalary heterochromatin and genetic silencing , 2003, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  Gerald M Rubin,et al.  Evidence for large domains of similarly expressed genes in the Drosophila genome , 2002, Journal of biology.

[15]  Ronald Berezney,et al.  Heterogeneity of eukaryotic replicons, replicon clusters, and replication foci , 2000, Chromosoma.

[16]  K. S. Egorova,et al.  The B-type lamin is required for somatic repression of testis-specific gene clusters , 2009, Proceedings of the National Academy of Sciences.

[17]  David Beare,et al.  Erratum: Replication timing of the human genome (Human Molecular Genetics) (2004) vol. 13 (191-202)) , 2004 .

[18]  D. Gilbert,et al.  Replication timing as an epigenetic mark , 2009, Epigenetics.

[19]  I. Zhimulev,et al.  Su(UR)ES: a gene suppressing DNA underreplication in intercalary and pericentric heterochromatin of Drosophila melanogaster polytene chromosomes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[20]  I. Makunin,et al.  Genomic analysis of Drosophila chromosome underreplication reveals a link between replication control and transcriptional territories. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Stephen M. Mount,et al.  The genome sequence of Drosophila melanogaster. , 2000, Science.

[22]  J. Dow,et al.  Using FlyAtlas to identify better Drosophila melanogaster models of human disease , 2007, Nature Genetics.

[23]  K. Hägele,et al.  Correspondence of banding patterns to 3H-thymidine labeling patterns in polytene chromosomes , 1976, Chromosoma.

[24]  R George,et al.  An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. , 1999, Genetics.

[25]  I. Simon,et al.  Developmental regulation of DNA replication timing at the human β globin locus , 2001 .

[26]  Charles Kooperberg,et al.  Genome-wide DNA replication profile for Drosophila melanogaster: a link between transcription and replication timing , 2002, Nature Genetics.

[27]  I. Simon,et al.  Developmental regulation of DNA replication timing at the human beta globin locus. , 2001, The EMBO journal.

[28]  Owen T McCann,et al.  Replication timing of the human genome. , 2004, Human molecular genetics.