These fine-tuned protein complexes don't tolerate mutations

Cohesin and Mediator protein complexes regulate cell type specific DNA loop structures to control gene expression

http://wi.mit.edu/news/archive/2010/surprise-genome-structure-linked-developmental-diseases

Excerpt: "Each cell type, such as skin cells, nerve cells, or embryonic stem cells, has its own gene expression program to maintain its cell state. For gene activation, transcription factors and gene expression machinery (RNA polymerase), bound to two different parts of the DNA called the promoter and the enhancer, must come in contact. This contact, which is facilitated and maintained by protein complexes called Mediator and Cohesin, forms a set of DNA loops that is specific to each cell type.

Problems with this DNA loop structure can interfere with the activation of cell-type-specific genes, which can cause the cell to lose its normal state. Indeed, mutations in Mediator and Cohesin, the protein complexes that contribute to DNA loop formation, at cell-type-specific genes, can cause various developmental syndromes and diseases, including Opitz-Kaveggia syndrome, Lujan syndrome and Cornelia de Lange syndrome.

According to the Young lab’s paper, published online in Nature this week, a DNA loop formed at the beginning of cell-type-specific genes enables activation of these genes. Each cell type, such as skin cells, nerve cells, or embryonic stem cells, has its own gene expression program to maintain its cell state. For gene activation, regulatory factors and gene expression machinery, bound to two different parts of the DNA called the promoter and the enhancer, must come in contact. This contact, which is facilitated and maintained by protein complexes called Mediator and Cohesin, forms a set of DNA loops that is specific to each cell type.

“That’s such a surprise,” says Young, whose lab is deciphering the overall cellular circuitry required to regulate gene expression and cell state. “We thought that a loop of DNA probably formed at the beginning of some genes—it’s an old model—but we didn’t expect that loops are formed by these complexes at active cell-type-specific genes.”
 

Problems with this DNA loop structure can interfere with the activation of cell-type-specific genes, which can cause the cell to lose its normal state. Indeed, mutations in Mediator and Cohesin, the protein complexes that contribute to DNA loop formation, at cell-type-specific genes, can cause various developmental syndromes and diseases."

http://www.sciencemag.org/news/2017/10/watch-human-genome-fold-itself-four-dimensions

Excerpt: "But cohesin really only affects looping that brings genes on the same chromosome into contact. A second, still-undefined mechanism seems to bring genes from different chromosomes together, the team notes. The changing landscape of loops helps cells quickly change which genes are active."

My comment: The cell uses these protein complexes for bringing genes into contact so that gene expression is perfectly controlled. The 3D landscape is efficiently changed along the needs of adaptation or cellular differentiation program. There are several epigenetic factors affecting this 3D looping: The DNA methylation, histone markings and non coding RNA molecules. Mutations in these fine-tuned protein complexes are associated with various developmental syndromes and diseases.

These mechanisms show us again that the DNA is not controlling cellular processes. Instead, the cell uses DNA genes as it needs them for achieving its goals. These sophisticated mechanisms point to Intelligent Design and Creation.