Transcription Factor Networks in Embryonic and Neural Stem Cells:

Abstract

The genetic material of any organism is also referred to as the genome and is passed on from generation to generation. The genome contains the hereditary information that is needed to construct the organism and to ensure its survival. This information is encoded in the form of deoxyribonucleic acid (DNA). DNA consists of two complementary strands of consecutively arranged nucleotides, composed of the nucleobase adenine (A), thymine (T), guanine (G) or cytosine (C). Due to selective pairing (A pairs to T, and G to C) they form a double helical structure which was first revealed by Watson and Crick in 1953 1. This discovery led to a revolution in genomic research that over 50 years later resulted in the first sequenced draft of the human genome 2. The diploid human genome comprises roughly 2 x 3 billion nucleotides which are divided over 22 paired chromosomes and the two sex chromosomes. In the genome are units, referred to as genes, that code for proteins or non-coding RNA molecules. Expression of genes varies between cell types and during the various stages of development of an organism. Therefore gene expression is temporally and spatially controlled by a myriad of regulatory mechanisms. This chapter will introduce the basic concepts of gene expression and review the current knowledge on how transcription can be regulated. It will highlight recent advances made on the identification of regulatory elements throughout the genome with the aid of post-translational modifications (PTMs) on chromatin. The second part of the introduction will focus on embryonic stem cells (ESCs) and neural stem cells (NSCs). Their origin and function will be discussed, including the potential these cells have for application in hypothesis-driven fundamental research. The role of the transcription factor Sox2 in both of these cell types will get specific attention.