ABSTRACT
Templates ......................................................................................211 8.3 Discussion .................................................................................... 212 8.4 Results .......................................................................................... 215 8.4.1 Colocalization of CTCF and H3K9me3 in the Human
Genome ........................................................................................ 215 8.4.2 IGF2BP1 Alleles are Stochastically Expressed in
Human B Cells ............................................................................. 215 8.4.3 CTCF Binds to its Target Motif at the IGF2BP1 Locus
Independently of DNA Methylation ............................................ 219
8.4.4 CTCF and H3K9me3 Colocalize at Both the Maternal and Paternal IGF2BP1 Alleles ..................................................... 224
8.4.5 The IGF2BP1 Promoter Associates with Both Active and Silent Histone Modifications in B Cells ............................... 227
8.4.6 Silencing of the Inactive IGF2BP1 Allele by Inhibition of RNA Polymerase II Elongation ............................................... 228
8.5 Conclusion ................................................................................... 231 Keywords .............................................................................................. 232 Acknowledgment .................................................................................. 232 Competing Interests .............................................................................. 232 Authors’ Contributions .......................................................................... 233 References ............................................................................................. 233 Credits ................................................................................................... 237
8.1 INTRODUCTION
Allele-specific gene expression is an integral component of cellular programming and development and contributes to the diversity of cellular phenotypes [1, 2]. Allelic differences in gene expression are mediated by either parent-of-origin-specific selection (imprinting) or stochastic selection of alleles for activation and/or silencing. The importance of genomic imprinting has recently been highlighted by RNA sequencing studies that demonstrated widespread allelic differences in gene expression in mouse brain affecting more than 1,300 genes [3]. The extent of sex-and stagespecific expression of individual alleles emphasizes the essential role of allelic transcriptional regulation in development. In addition to the extensive occurrence of imprinted parent-of-origin-specific expression, gene expression patterns of clonal cell populations are also modified by random or stochastic silencing of either the maternal or paternal allele. Wellknown loci displaying allele-specific expression include odorant receptor genes, immunoglobulins and various receptor proteins [4-6]. Additionally, previous large-scale studies have provided new data demonstrating that parent-of-origin-specific expression is employed much more frequently than previously thought [7]. These new findings illustrate the scale and
complexity of genomic allele-specific expression. However, the precise molecular mechanism underlying the allelic bias in gene expression is not very well understood.
