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  Dosage Sensing, Threshold Responses, and Epigenetic Memory: A Systems Biology Perspective on Random X‐Chromosome Inactivation

Mutzel, V., & Schulz, E. G. (2020). Dosage Sensing, Threshold Responses, and Epigenetic Memory: A Systems Biology Perspective on Random X‐Chromosome Inactivation. Bioessays, 42(4): e1900163. doi:10.1002/bies.201900163.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-01A5-E Version Permalink: http://hdl.handle.net/21.11116/0000-0006-01A6-D
Genre: Journal Article

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Mutzel_2020.pdf (Publisher version), 768KB
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 Creators:
Mutzel, Verena1, Author              
Schulz, Edda G.1, Author              
Affiliations:
1Regulatory Networks in Stem Cells (Edda G. Schulz), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117286              

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Free keywords: X-chromosome inactivation; epigenetic memory; feedback loops; gene regulatory networks; mathematical modeling; monoallelic expression; toggle switch
 Abstract: X‐chromosome inactivation ensures dosage compensation between the sexes in mammals by randomly choosing one out of the two X chromosomes in females for inactivation. This process imposes a plethora of questions: How do cells count their X chromosome number and ensure that exactly one stays active? How do they randomly choose one of two identical X chromosomes for inactivation? And how do they stably maintain this state of monoallelic expression? Here, different regulatory concepts and their plausibility are evaluated in the context of theoretical studies that have investigated threshold behavior, ultrasensitivity, and bistability through mathematical modeling. It is discussed how a twofold difference between a single and a double dose of X‐linked genes might be converted to an all‐or‐nothing response and how mutually exclusive expression can be initiated and maintained. Finally, candidate factors that might mediate the proposed regulatory principles are reviewed.

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Language(s): eng - English
 Dates: 2020-03-19
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1002/bies.201900163
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Title: Bioessays
  Other : Bioessays
Source Genre: Journal
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Publ. Info: Cambridge, UK : Co. of Biologists
Pages: - Volume / Issue: 42 (4) Sequence Number: e1900163 Start / End Page: - Identifier: ISSN: 0265-9247
CoNE: https://pure.mpg.de/cone/journals/resource/954925499109