Chromatin Structure and Function in Neurospora


Eukaryotic genomes are partitioned into structurally and functionally distinct chromatin domains. This image shows the arrangement of euchromatin (green) and heterochromatin (red) domains in N. crassa nuclei.

We are interested in understanding epigenetic and chromatin-based mechanisms that contribute to genome function and genome stability. In eukaryotes, chromosomal DNA is packaged with histone and non-histone proteins into chromatin. In the cell, this complex of DNA and protein is the relevant substrate for essential processes including transcription, DNA replication and DNA repair.

These processes are profoundly influenced by local chromatin structure, which is modulated by covalent modification of histone proteins, incorporation of histone variants, and in some organisms, methylation of cytosine bases in DNA. We are particularly interested in understanding how formation of repressive chromatin structures contributes to proper maintenance of genome stability (i.e. DNA replication and repair).

Chromatin modifications establish functionally distinct chromatin environments. H3 lysine-9 methylation (blue), H3 lysine-27 methylation (green), and H3 lysine-4 methylation establish different chromatin architectures to regulate genome functions.

We recently showed that two conserved histone methyltransferases, KMT1 and KMT6, have opposing effects on genome stability in the model fungus Neurospora crassa. These enzymes methylate histone H3 at specific lysine residues to establish two types of repressive chromatin.  In mammals, homologs of these enzymes are critical for development and defective function of  KMT6 has been tightly linked to cancer, but much is unknown about how they are regulated and how they function. Neurospora crassa is one of the simplest model systems that encodes both KMT1 and KMT6. Our work is focused on understanding these important enzymes. For all of our studies, we rely heavily on molecular, genetic, genomic, and proteomic methods.

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