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Dynamic Control of X Chromosome Conformation and Repression by a Histone H4K20 Demethylase.

Cell | Sep 21, 2017

Chromatin modification and higher-order chromosome structure play key roles in gene regulation, but their functional interplay in controlling gene expression is elusive. We have discovered the machinery and mechanism underlying the dynamic enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during C. elegans dosage compensation and demonstrated H4K20me1's pivotal role in regulating higher-order chromosome structure and X-chromosome-wide gene expression. The structure and the activity of the dosage compensation complex (DCC) subunit DPY-21 define a Jumonji demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals. Selective inactivation of demethylase activity eliminates H4K20me1 enrichment in somatic cells, elevates X-linked gene expression, reduces X chromosome compaction, and disrupts X chromosome conformation by diminishing the formation of topologically associating domains (TADs). Unexpectedly, DPY-21 also associates with autosomes of germ cells in a DCC-independent manner to enrich H4K20me1 and trigger chromosome compaction. Our findings demonstrate the direct link between chromatin modification and higher-order chromosome structure in long-range regulation of gene expression.

Pubmed ID: 28867287 RIS Download

Mesh terms: Amino Acid Sequence | Animals | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Carrier Proteins | Dosage Compensation, Genetic | Embryo, Nonmammalian | Gene Expression Regulation | Jumonji Domain-Containing Histone Demethylases | Models, Molecular | Mutation | Piperidines | Sequence Alignment | Thiophenes | X Chromosome

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Associated grants

  • Agency: NIGMS NIH HHS, Id: F32 GM100647
  • Agency: NIGMS NIH HHS, Id: R01 GM030702
  • Agency: NIH HHS, Id: S10 OD018174

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A Python package that provides infrastructure to process data from high-throughput sequencing assays. While the main purpose of HTSeq is to allow you to write your own analysis scripts, customized to your needs, there are also a couple of stand-alone scripts for common tasks that can be used without any Python knowledge.

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