5.19: Chromatin Position Affects Gene Expression
Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of gene expression in eukaryotes. For example, the gene promoters are organized physically separate from their regulatory DNA elements, such as enhancers. These promoter-enhancer elements need to be brought together to carry out gene expressions. Each chromatid comprises several such interacting units, termed as Topologically associated domains (TADs). In some instances, TADs from two chromatids may also interact with each other.
Chromosome Territories (CT)
Several TADs accumulate to form the chromosomal territories (CT). These spatial arrangements and distributions make nucleus a heterogeneous body with distinct biochemical activities. The positioning of genes inside the CT and the positioning of CTs itself affects gene expression. In humans, the actively transcribed genes tend to localize towards the periphery of their CT. Noncoding genes tend to localize towards their CTs interior. For example, in the human female amniotic fluid cell nuclei, the ANT2 gene is found on the inactive X chromosome. When the ANT2 gene is localized towards the periphery of CT, it results in its active transcription.
Chromatins are dynamically repositioned inside the nucleus. Even the terminally differentiated cells that can no longer divide exhibit chromatin or gene repositioning. This means that the repositioning is not a random event but a coordinated molecular mechanism.