Genomic approaches towards finding cis -regulatory modules (CRM) in - - PowerPoint PPT Presentation

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Genomic approaches towards finding cis -regulatory modules (CRM) in - - PowerPoint PPT Presentation

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Genomic approaches towards finding cis -regulatory modules (CRM) in animals Matthew I. Omoruyi 21.01.2013 www.helsinki.fi/yliopisto 1.11.2018 1 Introduction CRM is a stretch of DNA, usually 100 1000 DNA base pairs in length, where a

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Genomic approaches towards finding cis-regulatory modules (CRM) in animals

Matthew I. Omoruyi 21.01.2013

1.11.2018 1

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CRM is a stretch of DNA, usually 100 – 1000 DNA base pairs in length, where a number of transcription factors can bind and regulate expression of nearby genes

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Introduction

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They are typically located on the same DNA as the gene they control (cis) CRM includes, but not limited to the following

 Locus control regions  Promoters  Enhancers  Silencers  Boundary  Control elements and  Other modulators

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Introduction

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The development of animals from zygote to adults requires the expression of a specific set of genes at each developmental stage

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Typical examples in understanding gene expression

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The differentiation of cells into distinct tissues and organs also requires the expression of a specific set of genes in each cell types

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Gene expression

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Importance of CRM

  • 1. Expand our understanding of biology
  • 2. Application in medicine (susceptibility to

diseases)

  • 3. Proper understanding of evolution
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1. Searching genomic DNA for clusters of motifs that are needed for the specific binding of transcription factors 2. Comparing homologous, non-coding DNA sequences between related species 3. Direct assays for DNA sequences with epigenetic features that are characteristic of regulatory regions

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Methods used in predicting CRM in animals

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http://www.ncbi.nlm.nih.gov/PMGifs/Genomes/micr.html

  • The whole-genome sequences for over 85

microorganisms

  • Humans, and a handful of other eukaryotic
  • rganisms

Combination of results from database similarity searches and gene-predicting algorithms to identify coding sequences with good but not complete accuracy

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Information to help understand the methods

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Softwares

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How is this done?

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1. Searching genomic DNA for clusters of motifs that are needed for the specific binding of transcription factors

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Methods used in predicting CRM in animals

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2. Comparing homologous, non-coding DNA sequences between related species

By comparing the genomic sequences of species at different evolutionary distances, one can identify coding sequences and conserved non-coding sequences with regulatory functions and determine which sequence are unique for a given specie

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3. Direct assays for DNA sequences with epigenetic features that are characteristic of regulatory regions

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Epigenetic features are reversible features on a cell’s DNA that affect gene expression without altering DNA It is based on high-throughput sequencing and mapping to reference genomes

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Pros and cons

Searching genomic DNA for clusters of motifs that are needed for the specific binding of transcription factors Comparing homologous, non-coding DNA sequences between related species Direct assays for DNA sequences with epigenetic features that are characteristic of regulatory regions

1. Partial success under favourable conditions 2. Only small subset of CRMs is likely to be discovered by extreme evolutionary constraint 3. Does not work equally in all tissues 4. No sufficient specificity 5. Not designed to find CRMs that are active in only 1 specie or that are changing in a lineage specific manner 1. Partial success under favourable conditions 2. Only small subset of CRMs is likely to be discovered by extreme evolutionary constraint 3. Does not work equally in all tissues 4. No sufficient specificity 5. Not designed to find CRMs that are active in only 1 specie or that are changing in a lineage specific manner

  • 1. Epigenetic marks must be

mapped in tissues and at times of development that are informative to the question at hand

  • 2. May be bias.
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  • Cis-regulatory modules are DNA sequence

required to regulate gene expression

  • The genome of both prokaryotes and

eukaryotes are available in a vast number

  • f databases
  • These databases are used to predict the

DNA sequence required for gene expression by different methods

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Summary/conclusion

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Given the limitations of methods based on sequence motifs and comparative genomics, direct measurement of diagnostic epigenetic features should lead to improved methods for CRM prediction. Particular epigenetic features are highly correlated with CRMs, and progress is being made in finding combinations of these features that may distinguish different types of CRM.

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Summary/conclusion

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