Milking the Genome

Milking The Genome: The Bovine Genome Sequence Annotation Effort and Epigenomics of Lactation

Bovine Genome Annotation Effort. (Bovine Genome consortium)
The Bovine Genome Sequencing Consortium has organized community driven manual gene model annotation. The overall objective is to generate the best possible set of gene models, and connect them to biological function, focusing on genes that are of particular interest in bovine biology, such as lactation. This is achieved by involving researchers that are experts or interested in particular genes, gene systems or biological processes. The 210 participants are members of the Bovine Genome Sequencing Consortium, and are working together in analyzing the biology of the bovine genome; several will be present at the Int’l Milk genomics Symposium.

These researchers are annotating the bovine genome by confirming or making corrections to the exon/intron/UTR structure of predicted genes and submitting functional information. Annotations are submitted to the annotation submission database at BovineGenome.org. The submission database will be open until November 30, 2007. Participants are divided into working groups, based on themes of interest in bovine biology. I will give an interim update on the annotation efforts and findings of the lactation-working group.

Epigenomics of lactation
(Courtneay Freeman-Zadrowski1, Violeta Chen1, Elena Kabotyanski2, Jeffrey M Rosen2 and Monique Rijnkels1. 1USDA/ARS Children’s Nutrition Research Center, Dept. of Pediatrics-nutrition, 2Dept of Molecular and Cellular biology, Baylor College of Medicine, 1100 Bates street, Houston, TX77030, USA)

The effects of endocrine, autocrine and paracrine pathways on growth and morphological changes during functional development of the mammary gland have been studied extensively. Gene-expression-profiles specific for different stages of mammary gland development and differentiation have been identified. The hormonal signaling pathways and a number of the factors involved in local transcriptional regulation of milk protein genes have been uncovered. However, the mechanisms by which these genes are regulated epigenetically (in the context of chromatin conformation), to define functional differentiation of the gland have received very little attention.

To determine the role chromatin conformation has in the regulation of milk protein gene expression we are investigating how different markers of chromatin conformation change in the genomic domains harboring milk protein genes during the functional development (milk protein gene expression) of the mammary gland. Histone modifications indicate open and active, or closed and inactive chromatin. DNAseI hypersensitive sites indicating regions in chromatin that are more open and potentially represent regulatory elements. DNA methylation (the presence of 5-methylcytosine in CpG dinucleotides) indicates a closed inactive chromatin conformation. Chromatin Immuno-Precipitation (ChIP), DNase I, DNA methylation and chromatin conformation capture (3C) assays are being used to identify the presence of certain histone modifications, DNase I hypersensitivity (HS) and DNA methylation status, and interactions of regulatory regions respectively as a function of the developmental stage and tissue type.

We detect tissue- and developmental stage specific changes in chromatin conformation on milk protein gene promoters and potential distal regulatory elements. These changes indicate a progressive opening of the chromatin, which eventually leads to full functionality and expression of the milk protein genes. The observed chromatin changes imply the intersection of the hormonal signaling pathways of development with chromatin remodeling and epigenetic regulation during mammary gland development and functional differentiation.