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The first minute of gene activation


Mon, 28/03/2011 - 23:01

The first minute of gene activation

Researchers from the Chromatin and Gene Expression laboratory of the Centre for Genomic Regulation in Barcelona have discovered a mechanism which enables access to the information found in the DNA compacted in chromatin.
The discovery, published in the journal Genes and Development, reveals how steroid hormones induce DNA decompaction, allowing access to the information and driving cell proliferation.
In order to perform different functions and obtain specific proteins for each function, human cells control gene expression via transcription factors. These transcription factors are capable of recognising the instructions they find in the DNA sequence of our genome. These instructions, however, are difficult to access as the DNA is compacted in chromatin. Chromatin is the collection of DNA, histones and other proteins found in the nucleus of eukaryotic cells. Histones are the proteins over which fragments of DNA are wound in order to keep them compacted. There is one kind of histone, H1, which has been associated with transcription repression as it compacts the chromatin, limiting transcription factor access.
To find out how transcription factors gain access to the DNA in chromatin, the group of Miguel Beato has, for several years, been looking at gene activation by steroid hormones. These hormones act through receptors which are transcription factors. The hormone binding changes the shape of the receptor which allows it join to sequences in the DNA containing target genes..
The working group of Dr. Beato has described, in a recent study published in the journal Genes & Development, that only one minute after adding progesterone to breast cancer cells, a complex mechanism is activated which remodels the chromatin, displacing histone H1 and, in this way, allows access to the genes. This requirement is indispensable for permitting access to the genome information and also for cell proliferation. “These results reveal an unexpected complexity in the first steps of gene activation which drive chromatin decompaction” explains Miguel Beato, principal investigator of the study and coordinator of the Gene Regulation programme of the Centre for Genomic Regulation. “In our group we had already described some crucial processes for the regulation of gene expression but this discovery lets us understand how everything starts and gives us the tools for finding new strategies to control breast cancer development," adds Beato.
The work also demonstrates that progesterone stimulates the proliferation of breast cancer cells by a mechanism dependent on the NURF remodelling mechanism. This discovery means that NURF therefore becomes a potential target for controlling the development of hormone-dependant cancer.
Notes to the editor:
** Reference work: Guillermo Pablo Vicent, A. Silvina Nacht, Jofre Font-Mateu, Giancarlo Castellano, Laura Caveglia, Cecilia Ballaré, and Miguel Beato. Four enzymes cooperate to displace histone H1 during the first minute of hormonal gene activation. Genes and Development (2011).
** Acknowledgements: This work is funded by awards from the Department of Innovation, Universities and Business of the Catalan Government, the Ministry of Science and Innovation, Consolider, the Fund for Health Research and the EU HEROIC IP. Guillermo Pablo Vicent also has a Ramón y Cajal grant.
For further information: Laia Cendrós, Centre for Genomic Regulation (CRG). Tel. +34 93 316 02 37.