Title

Regulation and Evolution of X-linked Lymphocyte Regulated 3b

Date of Completion

January 2012

Keywords

Biology, Molecular|Biology, Genetics

Degree

Ph.D.

Abstract

Unlike autosomal genomic imprinting, the epigenetic marks at X-linked imprinting loci are not well characterized. No differentially methylated regions or antisense non-coding transcripts have been identified. This study provides evidence that the X-linked imprinted gene X-linked Lymphocyte Regulated 3b is not paternally silenced by preventing promoter recognition or pre-initiation complex assembly. Instead a mechanism of co-transcriptional gene silencing is suggested. In addition to showing a failure of RNA Polymerase II transit across the paternal copy, this work provides the first data supporting allele-specific alternative splicing. This establishes a mechanistic model incorporating the known epigenetic status of the locus with differences in transcript abundance, and arriving at the observed imprinted expression pattern. ^ This work also places the genomic imprinting of genes at this cluster in an evolutionary context. Examination of amino acid sequences suggests a subfamily of genes rapidly diverging from an ancestral protein that is otherwise remarkably conserved across metazoa. The multiply repeated structure of these genes in mouse is shown to be a recent and species specific feature. This study provides strong evidence for diversifying selection at the Xlr3/4/5 genes. ^