PXD046904

PXD046904 is an original dataset announced via ProteomeXchange.

Title	MeCP2 Represses the Activity of Topoisomerase IIβ in Long Neuronal Genes
Description	A unique signature of neuronal transcriptomes is the high expression of the longest genes in the genome (e.g. >100 kilobases). These genes encode proteins with essential functions in neuronal physiology, and disruption of long gene expression has been implicated in neurological disorders. DNA topoisomerases resolve topological constraints that arise on DNA and facilitate the expression of long genes in neurons. Conversely, methyl-CpG binding protein 2 (MeCP2), which is disrupted in Rett syndrome, can act as a transcriptional repressor to downregulate the expression of long genes. The molecular mechanisms underlying the regulation of long genes by these factors are not fully understood, however, and whether or not they directly influence each other is not known. Here, we identify a functional interaction between MeCP2 and Topoisomerase II-beta (TOP2β) in neurons. We show that MeCP2 and TOP2β physically interact in vivo and map protein sequences sufficient for their physical interaction in vitro. We profile TOP2β activity genome-wide in neurons and detect enrichment at regulatory regions and gene bodies of long neuronal genes, including long genes regulated by MeCP2. Further, we find that knockdown and overexpression of MeCP2 leads to altered TOP2β activity at MeCP2-regulated genes. Our findings uncover a mechanism by which MeCP2 inhibits the activity of TOP2β at long genes in neurons and suggest that this mechanism is disrupted in neurodevelopment disorders caused by mutation of MeCP2.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:14:28.692.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yoshiho Ikeuchi
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-13 07:06:28	ID requested
1	2023-11-15 05:40:55	announced
⏵ 2	2024-10-22 06:14:29	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Neuron, MeCP2, immunoprecipitation

Harrison Gabel
contact affiliation	Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA
contact email	gabelh@wustl.edu
lab head
Yoshiho Ikeuchi
contact affiliation	Washington University in St. Louis
contact email	yikeuchi@iis.u-tokyo.ac.jp
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046904
     1. Label: PRIDE project
     2. Name: MeCP2 Represses the Activity of Topoisomerase IIβ in Long Neuronal Genes