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Series GSE166423

Query DataSets for GSE166423

Status

Public on Sep 01, 2021

Title

5-hydroxymethylcytosine is required for terminal differentiation of Purkinje neurons

Organism

Experiment type

Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Methylation profiling by high throughput sequencing

Summary

Principal neurons in the mammalian brain exit cell cycle and execute a complex and prolonged differentiation program that continues into early adult life. Although high levels of 5-hydroxymethylcytosine (5hmC) accumulate in neurons, it is not known whether 5hmC can serve as an intermediate in DNA demethylation in postmitotic neurons. Here we report high resolution mapping of DNA methylation and hydroxymethylation, chromatin accessibility, and activating and repressive histone marks in developing postmitotic Purkinje cells (PCs). Our data reveal new relationships between PC transcriptional and epigenetic programs, and identify a class of late expressed genes that lose both 5mC and 5hmC during terminal differentiation. Deletion of the 5hmC writers Tet1, Tet2, and Tet3 from postmitotic Purkinje cells prevents loss of 5mC and 5hmC in regulatory domains and gene bodies and hinders transcriptional and epigenetic developmental transitions, resulting in hyper-excitability and increased susceptibility to excitotoxic drugs. Our data demonstrate that Tet-mediated active DNA demethylation occurs in vivo, and that acquisition of the precise molecular and electrophysiological properties of adult PCs requires continued oxidation of 5mC to 5hmC during the final phases of differentiation.

Overall design

RNA-Seq, ATAC-Seq, ChIP-Seq, OxBS-Seq, BS-Seq

Contributor(s)

Stoyanova E, Riad M, Rao A, Heintz N

Citation(s)

Submission date

Feb 09, 2021

Last update date

Jan 07, 2022

Contact name

Elitsa Stoyanova

E-mail(s)

estoyanova@rockefeller.edu

Organization name

Rockefeller University

Department

Molecular Biology

Lab

Heintz

Street address

1230 York Ave

City

NYC

State/province

NY

ZIP/Postal code

10065

Country

USA

Platforms (1)

Illumina NextSeq 500 (Mus musculus)

Samples (42)

More...

GSM5070935	Purkinje cell p0 RNA-Seq WT rep1
GSM5070936	Purkinje cell p0 RNA-Seq WT rep2
GSM5070937	Purkinje cell p7 RNA-Seq WT rep1

GSM5070938	Purkinje cell p7 RNA-Seq WT rep2
GSM5070939	Purkinje cell p56 RNA-Seq WT rep1
GSM5070940	Purkinje cell p56 RNA-Seq WT rep2
GSM5070941	Purkinje cell p0 ATAC-Seq WT rep1
GSM5070942	Purkinje cell p0 ATAC-Seq WT rep2
GSM5070943	Purkinje cell p7 ATAC-Seq WT rep1
GSM5070944	Purkinje cell p7 ATAC-Seq WT rep2
GSM5070945	Purkinje cell p56 ATAC-Seq WT rep1
GSM5070946	Purkinje cell p56 ATAC-Seq WT rep2
GSM5070947	Purkinje cell p0 ChIP-Seq H3K4me3 WT rep1
GSM5070948	Purkinje cell p0 ChIP-Seq H3K4me3 WT rep2
GSM5070949	Purkinje cell p7 ChIP-Seq H3K4me3 WT rep1
GSM5070950	Purkinje cell p7 ChIP-Seq H3K4me3 WT rep2
GSM5070951	Purkinje cell p56 ChIP-Seq H3K4me3 WT rep1
GSM5070952	Purkinje cell p56 ChIP-Seq H3K4me3 WT rep2
GSM5070953	Purkinje cell p0 ChIP-Seq H3K27me3 WT rep1
GSM5070954	Purkinje cell p0 ChIP-Seq H3K27me3 WT rep2
GSM5070955	Purkinje cell p7 ChIP-Seq H3K27me3 WT rep1
GSM5070956	Purkinje cell p7 ChIP-Seq H3K27me3 WT rep2
GSM5070957	Purkinje cell p56 ChIP-Seq H3K27me3 WT rep1
GSM5070958	Purkinje cell p56 ChIP-Seq H3K27me3 WT rep2
GSM5070959	Purkinje cell p0 OxBS-Seq WT rep1
GSM5070960	Purkinje cell p0 OxBS-Seq WT rep2
GSM5070961	Purkinje cell p7 OxBS-Seq WT rep1
GSM5070962	Purkinje cell p7 OxBS-Seq WT rep2
GSM5070963	Purkinje cell p56 OxBS-Seq WT rep1
GSM5070964	Purkinje cell p56 OxBS-Seq WT rep2
GSM5070965	Purkinje cell p0 BS-Seq WT rep1
GSM5070966	Purkinje cell p0 BS-Seq WT rep2
GSM5070967	Purkinje cell p7 BS-SeqWT rep1
GSM5070968	Purkinje cell p7 BS-Seq WT rep2
GSM5070969	Purkinje cell p56 BS-Seq WT rep1
GSM5070970	Purkinje cell p56 BS-Seq WT rep2
GSM5070971	Purkinje cell p56 OxBS-Seq Pcp2-Cre::Tet1-/-/Tet2-/-/Tet3-/- rep1
GSM5070972	Purkinje cell p56 BS-Seq Pcp2-Cre::Tet1-/-/Tet2-/-/Tet3-/- rep1
GSM5070973	Purkinje cell p56 RNA-Seq Pcp2-Cre+::Tet1-/-/Tet2-/-/Tet3-/- rep1
GSM5070974	Purkinje cell p56 RNA-Seq Pcp2-Cre+::Tet1-/-/Tet2-/-/Tet3-/- rep2
GSM5070975	Purkinje cell p56 RNA-Seq Tet1fl/fl/Tet2fl/fl/Tet3fl/fl rep1
GSM5070976	Purkinje cell p56 RNA-Seq Tet1fl/fl/Tet2fl/fl/Tet3fl/fl rep2

Relations

BioProject

SRA

Download family	Format
SOFT formatted family file(s)	SOFT
MINiML formatted family file(s)	MINiML
Series Matrix File(s)	TXT

Supplementary file	Size	Download	File type/resource
GSE166423_ATAC-seq_broadPeaks.tar.gz	15.3 Mb	(ftp)(http)	TAR
GSE166423_ChIP-seq_broadPeaks.tar.gz	9.1 Mb	(ftp)(http)	TAR
GSE166423_OxBS-Seq_BS-Seq_bigWigs.tar.gz	1.6 Gb	(ftp)(http)	TAR
GSE166423_RAW.tar	1.2 Mb	(http)(custom)	TAR (of TXT)
SRA Run Selector
Raw data are available in SRA
Processed data provided as supplementary file

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