Evolution of the Vertebrate Gene Regulatory Network Controlled by the Transcriptional Repressor REST

Rory Johnson, et al., Evolution of the Vertebrate Gene Regulatory Network Controlled by the Transcriptional Repressor REST, Mol Biol Evol (2009) 26 (7): 1491-1507

We show that one-third of human RE1s are unique to primates: These sites recruit REST in vivo, target neural genes, and are under purifying evolutionary selection We observe a consistent and significant trend for more ancient RE1s to have higher affinity for REST than lineage-specific sites and to be more proximal to garget genes. Our results lead us to propose a model where new transcription factor binding sites are constantly generated throughout the genome; thereafter refinement of their sequence and location consolidates this remodeling of networks governing neural gene regulation.

The Genome Project-Write

Jef D. Boeke, et al., The Genome Project-Write, Science 10, 2016

The primary goal of HGP-write is to reduce the costs of engineering and testing large (0.1 to 100 billion base fairs) genomes in cell lines by over 1000-fold within 10 years.

I bet The Genome Project-EpiWrite will be followed.

Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells

Dimitri Conomos, et al., Variant repeats are interspersed throughout the telomeres and recruit nuclear receptors in ALT cells, J. Cell Biol. 199, 2012

Telomeres in cells that use recombination-mediated alternative lengthening of telomeres (ALT) pathway elicit a DNA damage response that is partly independent of telomere length.

Here we used next generation sequencing to analyze the DNA content of ALT telomeres. We discovered that variant repeats were interspersed throughout the telomeres of ALT cells. We found that the C-type (TCAGGG) variant repeat predominated and created a high-affinity binding site for the nuclear receptors COUP-TF2 and TR4.

We used next generation sequencing to quantitatively determine the identity and extent of variant sequence within telomere arrays of WI38-VA13/2RA as well as the telomerase-positive HeLa cell line. Samples were paired-end sequenced, and reads containing greater than six nonconsecutive telomeric repeats in the format TBAGGG were considered to be reads derived from telomeres.

Structure and Variability of Human Chromosome Ends

Titia de Lange, et al., Structure and Variability of Human Chromosome Ends, Molecular and Cellular Biology 10, 1990,

The minimal size of the subtelomeric repeat is 4 kilo bases (kb); it shows a high frequency of restriction fragment length polymorphisms and undergoes extensive de novo methylation in somatic cells. Distal to the subtelomeric repeat, the chromosomes terminate in a long region (up to 14kb) that may be entirely composed of TTAGGG repeats. This terminal segment is unusually variable. Although sperm telomeres are 10 to 14kb long, telomeres in somatic cells are several kilo base pairs shorter and very heterogeneous in length.

Human telomeres contain at least three types of G-rich repeat distributed non-randomly

Robin C. Allshire, et al., Human telomeres contain at least three types of G-rich repeat distributed non-randomly,  Nucleic Acids Research 17, 1989

Human telomeres do not contain a pure uniform 6 base pair repeat unit but that there are at least three types of repeat.

The distribution of each type of repeat appears to be non-random. Each human telomere has a similar arrangement of these repeats relative to the ends of the chromosome.

Analysing the change in length of the telomeric repeat region between an individuals blood and gremlin DNA reveals that this is due to variable amounts of the TTAGGG repeat and not the other repeat types.

There can only be, on average, a maximum of 8.3kb of TTAGGG like repeats per sperm telomere. In addition approximately 1.2kb of TTGGGG like repeats must be distal to all MnlI and HphI site. The most proximal 1.9kb of each telomeric repeat region is made up of TTGGGG and TGAGGG like repeats, this leaves approximately 3.6kb of the human telomeric repeat region unaccounted for.