Platform for analysis of gene regulation location

ChIP-on-chip analysis technique pinpoints activity at regulatory regions of genomes for insight into researching disease, therapies, and embryonic stem cells

Agilent Technologies has introduced its ChIP-on-chip microarray for analysing activity at regulatory regions of genomes.

The technology, also known as location analysis, provides insight into key mechanisms of embryonic stem cells and illnesses such as cancer, cardiovascular disease and central nervous system disorders.

Scientists can also use this technique to develop therapies.

'ChIP' refers to chromatin immunoprecipitation, and 'chip' refers to the glass slides on which the microarrays are printed.

"ChIP-on-chip is an example of Agilent's drive to develop the next generation of microarray applications," said Fran DiNuzzo, vice president and general manager of Agilent's integrated biology business.

"Emerging applications, coupled with the ability to design and print microarrays containing up-to-date content, are the foundation of our genomics programme".

"ChIP-on-chip goes beyond gene expression to explore gene regulation activity," said Richard Young, of MIT and its Whitehead Institute affiliate.

"Regulatory proteins bind to genomic DNA to control DNA replication and gene expression, thereby functioning as switches in the regulatory circuitry of cells.

"Combine this information with gene expression data and you get biomarkers".

On 8 September 2005, the early online edition of the journal Cell published a paper by researchers at Young's Whitehead Institute, describing how they used the technique to discover the mechanism by which human embryonic stem cells retain the ability to become any type cell, and how this ability is lost once the cells begin to differentiate.

The 26 August 2005, issue of Cell (Vol.

122, 517-527) also published a paper by researchers at the Young lab, describing how they used chromatin immunoprecipitation with DNA microarrays to produce genome-wide maps of acetylation and methylation - regulatory events - in yeast.

The lab studies yeast to construct testable models to predict how cellular processes are regulated at the transcription level by the proteins that control gene expression.

In January 2005, Agilent purchased Computational Biology, which was founded by Young to develop ChIP-on-chip technology.

He remains a consultant to Agilent, along with co-founders David Gifford and Heidi Wyle.

Agilent recently established a centre in Cambridge, USA, primarily to develop and support ChIP-on-chip and related applications.

Part of the value of Agilent's microarray products is access to the latest probe databases, it says.

The company's eArray online tool enables users to design their own custom microarrays and then print them on slides using Agilent's highly flexible SurePrint inkjet technology.

This empowers researchers to develop innovative applications in the highly dynamic genomics environment.

Young's team at the Whitehead Institute designed the probes and associated array layouts on the Agilent platform.

In addition to using yeast arrays, numerous researchers have been using Agilent mouse and human promoter and Encode arrays for ChIP-on-chip analysis since January 2005.

The probes are designed to offer broad genome coverage, allowing researchers to study regulatory events on a genome-wide scale.

"Analysing transcriptional regulation using location analysis microarrays is a major aspect of our research into the basic mechanism of lung fibrosis," said Naftali Kaminski, director of the Dorothy and Richard Simmons Center for Interstitial Lung Disease at the University of Pittsburgh School of Medicine.

"We consider it critical to be able to perform the hybridisations and visualise and analyse the results in our own lab.

"This provides us with immediate access to results, and the ability to troubleshoot day-to-day experiments rather than being dependent on batch analyses".

Referring to his usage of some of the mammalian designs, Brian Dynlacht, director of genomics programme for New York University's Cancer Institute, said, "We observe very impressive enrichment upon immunoprecipitation with these microarrays, and the dynamic range of the signal in the IP channel is excellent.

"The background signal is extremely low".

Agilent plans to offer a complete solution for location analysis that includes reagents, a microarray portfolio and data analysis software.

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