Genome complexity: controlling pleuropotency and differentia (Introduction)

by David Turell , Monday, June 05, 2017, 21:06 (2727 days ago) @ David Turell

Controlled by two genes who cross talk with each other:

https://phys.org/news/2017-06-genetic-cross-talk-key-cell.html

"Competing regulatory genes "talk" to each other to maintain balance of cell state, according to new research from the Stowers Institute for Medical Research.

"Stowers scientists Bony De Kumar, Ph.D., and Robb Krumlauf, Ph.D., provide evidence of direct cross-regulatory feedback, or cross-talk, between Nanog and Hox genes.

"Nanog and Hox genes regulate cell pluripotency and differentiation, respectively. When cells are pluripotent, they have the capacity to self-renew and the potential to change into any of a number of cell types. And when cells differentiate, they become a more specialized cell type, like heart, brain, or skin cells.

"In adult organisms, striking a balance between these two states is important to keep many tissues in equilibrium. The blood supply, for example, has cells that are differentiating, dying, or being repaired, and a reserve population of blood-producing adult stem cells is needed to help replace them.

"The Stowers study suggests that balance between pluripotency and differentiation hinges in part on regulatory communication involving inhibition between Nanog and Hox genes. Krumlauf compares this cross-talk to parents giving their children instructions.

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"Both positive and negative instructions are important. Nanog and Hox genes each have their own distinct jobs and by inhibiting each other they work together to direct the proper balance of cell states by helping the cell avoid wrong turns and stay on course.

"'Differentiation and pluripotency are well-studied processes," says first author De Kumar. "This paper actually links the processes together. Before, we did not know that these pathways were talking to each other. It was pretty surprising for us."

"The researchers made the discovery while studying Hox genes in the early stages of mouse embryonic stem cell differentiation. These "architect genes" control the layout of a developing embryo and play a key role in the establishment of the basic body plan and craniofacial development.

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"'Over the past 10 to 20 years, biologists have shown that cells are actively assessing their environment, and that they have many fates they can choose. The regulatory loops we've found show how the dynamic nature of cells is being maintained," says Krumlauf, who was recently inducted into the National Academy of Sciences for his seminal work on Hox genes.
The work provides important insight into the basic processes of tissue formation"

The article abstract:

http://www.pnas.org/content/early/2017/05/30/1610612114

"Homeobox a1 (Hoxa1) is one of the most rapidly induced genes in ES cell differentiation and it is the earliest expressed Hox gene in the mouse embryo. In this study, we used genomic approaches to identify Hoxa1-bound regions during early stages of ES cell differentiation into the neuro-ectoderm. Within 2 h of retinoic acid treatment, Hoxa1 is rapidly recruited to target sites that are associated with genes involved in regulation of pluripotency, and these genes display early changes in expression. The pattern of occupancy of Hoxa1 is dynamic and changes over time. At 12 h of differentiation, many sites bound at 2 h are lost and a new cohort of bound regions appears. At both time points the genome-wide mapping reveals that there is significant co-occupancy of Nanog (Nanog homeobox) and Hoxa1 on many common target sites, and these are linked to genes in the pluripotential regulatory network. In addition to shared target genes, Hoxa1 binds to regulatory regions of Nanog, and conversely Nanog binds to a 3′ enhancer of Hoxa1. This finding provides evidence for direct cross-regulatory feedback between Hoxa1 and Nanog through a mechanism of mutual repression. Hoxa1 also binds to regulatory regions of Sox2 (sex-determining region Y box 2), Esrrb (estrogen-related receptor beta), and Myc, which underscores its key input into core components of the pluripotential regulatory network. We propose a model whereby direct inputs of Nanog and Hoxa1 on shared targets and mutual repression between Hoxa1 and the core pluripotency network provides a molecular mechanism that modulates the fine balance between the alternate states of pluripotency and differentiation. "

Comment: Just more evidence of the interlocking feedback loops of balanced controls by genes as they automatically build an embryo. They contain information to do this. No innate intelligence required, even though they are acting intelligently.