chapter  2
- Vitamin D Receptor: Genomic and Epigenomic Effects
Pages 28

Complete sequencing in 1998 of the rst multicellular organism, Caenorhabditis elegans, revealed it to have about 19,000 genes. Surprisingly, completion of the human genome sequence several years later revealed just 4000 more genes [1]. Complexity, therefore, as measured by the number of different cell types and the behaviours of intra-and intercellular networks, clearly does not relate directly to the number of genes. It is revealing that, while the human genome encodes approximately 3000 transcription factors regulating 23,000 genes spread over 3300 mb of DNA, that of C. elegans encodes just 600 transcription factors, regulating 19,000 genes spread over 100 mb of DNA. Therefore, transcription factor numbers and gene spacing relate more closely to complexity than gene numbers [2]. Furthermore, the recent identication of genome-wide transcription even

2.1 Introduction ............................................................................................................................ 37 2.1.1 Transcriptional Control of the Human Genome ......................................................... 37 2.1.2 Epigenetic Events Control the Rate and Magnitude of Transcription ........................ 38 2.1.3 Higher Order Chromatin Interactions Associated with Transcription ....................... 39

2.2 VDR as a Member of the Nuclear Receptor Superfamily ......................................................40 2.2.1 Identication of the VDR ...........................................................................................40 2.2.2 Activation of the VDR by Ligand ............................................................................... 41 2.2.3 VDR Associates with Chromatin in Large Multimeric Complexes ........................... 41 2.2.4 VDR Signal Specicity............................................................................................... 42

2.2.4.1 Interactions with Corepressors and Coactivators......................................... 42 2.2.4.2 PTMs of the VDR Complex ........................................................................44