Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes

BackgroundGlobal regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group.ResultsIn the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes.ConclusionThe differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

[1]  E. Levanon,et al.  Human housekeeping genes are compact. , 2003, Trends in genetics : TIG.

[2]  C. Benham,et al.  Transcriptional augmentation: modulation of gene expression by scaffold/matrix-attached regions (S/MAR elements). , 2000, Critical reviews in eukaryotic gene expression.

[3]  Galina V. Glazko,et al.  Computer Prediction of Sites Associated with Various Elements of the Nuclear Matrix , 2000, Briefings Bioinform..

[4]  S. Brahmachari,et al.  Simple repetitive sequences in the genome: Structure and functional significance , 1995, Electrophoresis.

[5]  G. Glazko,et al.  Origin of a substantial fraction of human regulatory sequences from transposable elements. , 2003, Trends in genetics : TIG.

[6]  J Seth Strattan,et al.  Nucleosomes unfold completely at a transcriptionally active promoter. , 2003, Molecular cell.

[7]  A. E. Sippel,et al.  Dissection of the locus control function located on the chicken lysozyme gene domain in transgenic mice. , 1994, Nucleic acids research.

[8]  M Conrad,et al.  DNA structural variability as a factor in gene expression and evolution. , 1986, Bio Systems.

[9]  A. Vinogradov.  Compactness of human housekeeping genes: selection for economy or genomic design? , 2004, Trends in genetics : TIG.

[10]  G. Felsenfeld,et al.  The 5'-HS4 chicken beta-globin insulator is a CTCF-dependent nuclear matrix-associated element. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  T. Heidmann,et al.  A Nuclear Matrix/Scaffold Attachment Region Co-localizes with the Gypsy Retrotransposon Insulator Sequence* , 1998, The Journal of Biological Chemistry.

[12]  A. Wolffe.  Transcriptional Activation: Switched-on chromatin , 1994, Current Biology.

[13]  Jaeseung Yoon,et al.  Improved recombinant gene expression in CHO cells using matrix attachment regions. , 2004, Journal of biotechnology.

[14]  J. Griffith,et al.  The [(G/C)3NN]n motif: a common DNA repeat that excludes nucleosomes. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Tjian,et al.  Orchestrated response: a symphony of transcription factors for gene control. , 2000, Genes & development.

[16]  V. Corces,et al.  Visualization of chromatin domains created by the gypsy insulator of Drosophila , 2003, The Journal of cell biology.

[17]  Martin J. Lercher,et al.  Clustering of housekeeping genes provides a unified model of gene order in the human genome , 2002, Nature Genetics.

[18]  V. Babich,et al.  Clusters of regulatory signals for RNA polymerase II transcription associated with Alu family repeats and CpG islands in human promoters. , 2004, Genomics.

[19]  Victor G. Levitsky,et al.  Nucleosome formation potential of eukaryotic DNA: calculation and promoters analysis , 2001, Bioinform..

[20]  Eugene V Koonin,et al.  A significant fraction of conserved noncoding DNA in human and mouse consists of predicted matrix attachment regions. , 2003, Trends in genetics : TIG.

[21]  T. Petes,et al.  Control of Meiotic Recombination and Gene Expression in Yeast by a Simple Repetitive DNA Sequence That Excludes Nucleosomes , 1999, Molecular and Cellular Biology.

[22]  G. Längst,et al.  Chromatin higher order structure: opening up chromatin for transcription. , 2004, Briefings in functional genomics & proteomics.

[23]  B. Suter,et al.  Poly(dA.dT) sequences exist as rigid DNA structures in nucleosome-free yeast promoters in vivo. , 2000, Nucleic acids research.

[24]  Nick Gilbert,et al.  Chromatin Architecture of the Human Genome Gene-Rich Domains Are Enriched in Open Chromatin Fibers , 2004, Cell.

[25]  Frank Grosveld,et al.  Spatial organization of gene expression: the active chromatin hub , 2003, Chromosome Research.

[26]  S. Khorasanizadeh.  The Nucleosome From Genomic Organization to Genomic Regulation , 2004, Cell.

[27]  E. Pennisi.  Human genome. A low number wins the GeneSweep Pool. , 2003, Science.

[28]  V. Iyer,et al.  Poly(dA:dT), a ubiquitous promoter element that stimulates transcription via its intrinsic DNA structure. , 1995, The EMBO journal.

[29]  D. Moazed,et al.  Heterochromatin and Epigenetic Control of Gene Expression , 2003, Science.

[30]  H L Robinson,et al.  Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin , 1986, Journal of virology.

[31]  M. V. Glazkov,et al.  Comparative study and prediction of DNA fragments associated with various elements of the nuclear matrix. , 2001, Biochimica et biophysica acta.

[32]  H. Bussemaker,et al.  The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes. , 2003, Genome research.

[33]  D. Thiele,et al.  Functional Analysis of a Homopolymeric (dA-dT) Element That Provides Nucleosomal Access to Yeast and Mammalian Transcription Factors* , 1999, The Journal of Biological Chemistry.

[34]  Samir K. Brahmachari,et al.  Alu repeat analysis in the complete human genome: trends and variations with respect to genomic composition , 2004, Bioinform..

[35]  Deepak Grover,et al.  Nonrandom distribution of alu elements in genes of various functional categories: insight from analysis of human chromosomes 21 and 22. , 2003, Molecular biology and evolution.

[36]  S A Krawetz,et al.  Mathematical model to predict regions of chromatin attachment to the nuclear matrix. , 1997, Nucleic acids research.