Wrange Lab Profile

Research Focus:

Glucocorticoid Receptor Mediated Chromatin Remodeling

From yeast to man, the DNA in every living cell is packaged into a DNAprotein complex called chromatin, the smallest packaging unit of which is the nucleosome. Genes are sorted into inactive and active chromatin domains that are specific for each cell type. We are now learning that the histones of these different domains carry specific chemical modification. Some genes in active chromatin domains may be switched ON or OFF by regulatory proteins such as the glucocorticoid receptor. Genes in an inactive domain will however not be activated. This glucocorticoid receptor is regulated by glucocorticoid hormone. An early step in the gene-activation is the glucocorticoid receptor mediated recruitment of so called co-activators. These are large multiprotein complexes, some of which have enzymatic activities which are able of covalently modify the surrounding chromatin proteins (histones) and/or by ATP-dependent structural remodeling. During gene activation these processes typically result in a more relaxed chromatin that allows the gene to become transcribed. During gene silencing the chromatin is thought to be more densely packed and to become less accessible to regulatory proteins. The silencing process is characterized primarily by a specific pattern of histone methylation and recruitment of specific proteins such as heterochromatin protein 1 (HP1). The mechanistic and structural details of these events are only scarcely known and are the focus of our interest.

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