Dynamic Control of Chromosome Topology and Gene Expression by a Chromatin Modification

Cold Spring Harbor Symposia on Quantitative Biology
Qian BianBarbara J Meyer

Abstract

The function of chromatin modification in establishing higher-order chromosome structure during gene regulation has been elusive. We dissected the machinery and mechanism underlying the enrichment of histone modification H4K20me1 on hermaphrodite X chromosomes during Caenorhabditis elegans dosage compensation and discovered a key role for H4K20me1 in regulating X-chromosome topology and chromosome-wide gene expression. Structural and functional analysis of the dosage compensation complex (DCC) subunit DPY-21 revealed a novel Jumonji C demethylase subfamily that converts H4K20me2 to H4K20me1 in worms and mammals. Inactivation of demethylase activity in vivo by genome editing eliminated H4K20me1 enrichment on X chromosomes of somatic cells, increased X-linked gene expression, reduced X-chromosome compaction, and disrupted X-chromosome conformation by diminishing the formation of topologically associated domains. H4K20me1 is also enriched on the inactive X of female mice, making our studies directly relevant to mammalian development. Unexpectedly, DPY-21 also associates specifically with autosomes of nematode germ cells in a DCC-independent manner to enrich H4K20me1 and trigger chromosome compaction. Thus, DPY-21 is an adaptable c...Continue Reading

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Citations

Oct 27, 2018·Current Genetics·Matthew Robert PaulSevinç Ercan
May 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Qian BianBarbara J Meyer
Jan 6, 2019·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Lenka StixováEva Bártová
Nov 17, 2020·Physiological Genomics·Adriana Z Corvalan, Hilary A Coller

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Methods Mentioned

BETA
X-ray
immunoprecipitation
RNA-seq
Hi-C

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