Browse
Submit Data
Databases
API
Help

Dataset Information

31 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Circadian cycle-dependent MeCP2 and brain chromatin changes.

ABSTRACT: Methyl CpG binding protein 2 (MeCP2) is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian cycle. We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian-dependent regulation of well-stablished MeCP2 target genes. Furthermore, this data suggests that alterations of MeCP2 can be responsible for the sleeping disorders arising from pathological stages, such as in autism and Rett syndrome.

SUBMITTER: Martinez de Paz A

PROVIDER: S-EPMC4395115 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Circadian cycle-dependent MeCP2 and brain chromatin changes.

Martínez de Paz Alexia A Sanchez-Mut Jose Vicente JV Samitier-Martí Mireia M Petazzi Paolo P Sáez Mauricio M Szczesna Karolina K Huertas Dori D Esteller Manel M Ausió Juan J

PloS one 20150413 4

Methyl CpG binding protein 2 (MeCP2) is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian cycle. We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian- ...[more]

PMID: 25875630

Similar Datasets

Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2.

Project description:Despite their central importance in mammalian development, the mechanisms that regulate the DNA methylation machinery and thereby the generation of genomic methylation patterns are still poorly understood. Here, we identify the 5mC-binding protein MeCP2 as a direct and strong interactor of DNA methyltransferase 3 (DNMT3) proteins. We mapped the interaction interface to the transcriptional repression domain of MeCP2 and the ADD domain of DNMT3A and find that binding of MeCP2 strongly inhibits the activity of DNMT3A in vitro. This effect was reinforced by cellular studies where a global reduction of DNA methylation levels was observed after overexpression of MeCP2 in human cells. By engineering conformationally locked DNMT3A variants as novel tools to study the allosteric regulation of this enzyme, we show that MeCP2 stabilizes the closed, autoinhibitory conformation of DNMT3A. Interestingly, the interaction with MeCP2 and its resulting inhibition were relieved by the binding of K4 unmodified histone H3 N-terminal tail to the DNMT3A-ADD domain. Taken together, our data indicate that the localization and activity of DNMT3A are under the combined control of MeCP2 and H3 tail modifications where, depending on the modification status of the H3 tail at the binding sites, MeCP2 can act as either a repressor or activator of DNA methylation.

| S-EPMC6158614 | biostudies-literature

Chromatin context and ncRNA highlight targets of MeCP2 in brain.

Project description:The discovery that Rett syndrome (RTT) is caused by mutation of the methyl-CpG-binding-protein MeCP2 provided a major breakthrough in understanding the neurodevelopmental disorder and accelerated MeCP2 research. However, gene regulation by MeCP2 is complicated. The current consensus for MeCP2 remains as a classical repressor complex, with major emphasis on its role in methylation-dependent binding and repression. However, recent evidence indicates additional regulatory roles, suggesting non-classical mechanisms in gene activation. This has opened the field of MeCP2 research and suggests that the gene targets may not be the usual suspects, that is, dependent only on DNA methylation. Here we examine how chromatin binding and sequence preference may confer MeCP2 functionality, and connect relevant pathways in an active genome. Finding both genomic and proteomic evidence to indicate MeCP2 spliceosome interaction, we consequently discovered broad MeCP2 enrichment of the transcriptome while our focus toward long non-coding RNA (lncRNA) revealed MeCP2 association with RNCR3. Our data may indicate an as-yet-unappreciated role between lncRNA and MeCP2. We hypothesize that ncRNA may mediate chromatin-remodeling events by interacting with MeCP2, thereby conferring changes in gene expression. We consider that these results may suggest new mechanisms of gene regulation conferred by MeCP2 and its interactions upon chromatin structure and gene function.

| S-EPMC3907483 | biostudies-literature

Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping.

Project description:ATRX and MeCP2 belong to an expanding group of chromatin-associated proteins implicated in human neurodevelopmental disorders, although their gene-regulatory activities are not fully resolved. Loss of ATRX prevents full repression of an imprinted gene network in the postnatal brain and in this study we address the mechanistic aspects of this regulation. We show that ATRX binds many imprinted domains individually but that transient co-localization between imprinted domains in the nuclei of neurons does not require ATRX. We demonstrate that MeCP2 is required for ATRX recruitment and that deficiency of either ATRX or MeCP2 causes decreased frequency of long-range chromatin interactions associated with altered nucleosome density at CTCF-binding sites and reduced CTCF occupancy. These findings indicate that MeCP2 and ATRX regulate gene expression at a subset of imprinted domains by maintaining a nucleosome configuration conducive to CTCF binding and to the maintenance of higher order chromatin structure.

| S-EPMC4117782 | biostudies-literature

MeCP2: A Critical Regulator of Chromatin in Neurodevelopment and Adult Brain Function.

Project description:Methyl CpG binding protein 2 (MeCP2) was first identified as a nuclear protein with a transcriptional repressor role that recognizes DNA methylation marks. MeCP2 has a well-established function in neurodevelopment, as evidenced by the severe neurological impairments characteristic of the Rett syndrome (RTT) pathology and the MeCP2 duplication syndrome (MDS), caused by loss or gain of MeCP2 function, respectively. Research aimed at the underlying pathophysiological mechanisms of RTT and MDS has significantly advanced our understanding of MeCP2 functions in the nervous system. It has revealed, however, that MeCP2 has more varied and complex roles than previously thought. Here we review recent insights into the functions of MeCP2 in neurodevelopment and the less explored requirement for MeCP2 in adult brain function. We focus on the emerging view that MeCP2 is a global chromatin organizer. Finally, we discuss how the individual functions of MeCP2 in neurodevelopment and adulthood are linked to its role as a chromatin regulator.

| S-EPMC6769791 | biostudies-literature

Cell cycle-dependent chromatin and transcriptional changes

Project description:The cellular and nuclear states are constantly changing and closely linked to DNA replication and cell division, defining cell cycle phases. Pharmacological inhibition is a widely used strategy to enrich for specific phases to study them in isolation. However, it is important to understand how synchronization influences chromatin openness and gene expression compared to unperturbed cell cycle states. Here, we use an integrated approach to obtain G1, S and G2/M phases from mouse embryonic stem cells (mESC) and to profile their chromatin accessibility and marks as well as steady and nascent transcripts levels. We demonstrate that synchronization with thymidine and nocodazole leads to dramatic changes in chromatin compaction and gene expression, which only partially resemble bona fide cell cycle-dependent differences. Blocking with CDK1 inhibitor results in efficient synchronization and evokes moderate changes in chromatin accessibility, resembling G2/M phase. Correlative analysis suggests that cell cycle-specific variations in chromatin openness in unperturbed mESCs are mediated by CDK1 substrates and CTCF. This integrated strategy can be applied to most cultured cell lines under any conditions and holds the potential to further our understanding of cell cycle-dependent susceptibility to external cues and chromatin regulation.

2021-12-31 | GSE167963 | GEO

Cell cycle-dependent chromatin and transcriptional changes

Project description:Cell cycle-dependent chromatin and transcriptional changes

| PRJNA705689 | ENA

Clock-dependent chromatin topology modulates circadian transcription and behavior.

Project description:The circadian clock in animals orchestrates widespread oscillatory gene expression programs, which underlie 24-h rhythms in behavior and physiology. Several studies have shown the possible roles of transcription factors and chromatin marks in controlling cyclic gene expression. However, how daily active enhancers modulate rhythmic gene transcription in mammalian tissues is not known. Using circular chromosome conformation capture (4C) combined with sequencing (4C-seq), we discovered oscillatory promoter-enhancer interactions along the 24-h cycle in the mouse liver and kidney. Rhythms in chromatin interactions were abolished in arrhythmic Bmal1 knockout mice. Deleting a contacted intronic enhancer element in the Cryptochrome 1 (Cry1) gene was sufficient to compromise the rhythmic chromatin contacts in tissues. Moreover, the deletion reduced the daily dynamics of Cry1 transcriptional burst frequency and, remarkably, shortened the circadian period of locomotor activity rhythms. Our results establish oscillating and clock-controlled promoter-enhancer looping as a regulatory layer underlying circadian transcription and behavior.

| S-EPMC5900709 | biostudies-literature

Cell-Cycle-Dependent Chromatin Dynamics at Replication Origins.

Project description:Origins of DNA replication are specified by the ordered recruitment of replication factors in a cell-cycle-dependent manner. The assembly of the pre-replicative complex in G1 and the pre-initiation complex prior to activation in S phase are well characterized; however, the interplay between the assembly of these complexes and the local chromatin environment is less well understood. To investigate the dynamic changes in chromatin organization at and surrounding replication origins, we used micrococcal nuclease (MNase) to generate genome-wide chromatin occupancy profiles of nucleosomes, transcription factors, and replication proteins through consecutive cell cycles in Saccharomyces cerevisiae. During each G1 phase of two consecutive cell cycles, we observed the downstream repositioning of the origin-proximal +1 nucleosome and an increase in protected DNA fragments spanning the ARS consensus sequence (ACS) indicative of pre-RC assembly. We also found that the strongest correlation between chromatin occupancy at the ACS and origin efficiency occurred in early S phase, consistent with the rate-limiting formation of the Cdc45-Mcm2-7-GINS (CMG) complex being a determinant of origin activity. Finally, we observed nucleosome disruption and disorganization emanating from replication origins and traveling with the elongating replication forks across the genome in S phase, likely reflecting the disassembly and assembly of chromatin ahead of and behind the replication fork, respectively. These results provide insights into cell-cycle-regulated chromatin dynamics and how they relate to the regulation of origin activity.

| S-EPMC8701747 | biostudies-literature

Cyclin-dependent kinase inhibitor p20 controls circadian cell-cycle timing.

Project description:Specific stages of the cell cycle are often restricted to particular times of day because of regulation by the circadian clock. In zebrafish, both mitosis (M phase) and DNA synthesis (S phase) are clock-controlled in cell lines and during embryo development. Despite the ubiquitousness of this phenomenon, relatively little is known about the underlying mechanism linking the clock to the cell cycle. In this study, we describe an evolutionarily conserved cell-cycle regulator, cyclin-dependent kinase inhibitor 1d (20 kDa protein, p20), which along with p21, is a strongly rhythmic gene and directly clock-controlled. Both p20 and p21 regulate the G1/S transition of the cell cycle. However, their expression patterns differ, with p20 predominant in developing brain and peak expression occurring 6 h earlier than p21. p20 expression is also p53-independent in contrast to p21 regulation. Such differences provide a unique mechanism whereby S phase is set to different times of day in a tissue-specific manner, depending on the balance of these two inhibitors.

| S-EPMC3637774 | biostudies-literature

Cell cycle-dependent localization of the proteasome to chromatin.

Project description:An integrative understanding of nuclear events including transcription in normal and cancer cells requires comprehensive and quantitative measurement of protein dynamics that underlie such events. However, the low abundance of most nuclear proteins hampers their detailed functional characterization. We have now comprehensively quantified the abundance of nuclear proteins with the use of proteomics approaches in both normal and transformed human diploid fibroblasts. We found that subunits of the 26S proteasome complex were markedly down-regulated in the nuclear fraction of the transformed cells compared with that of the wild-type cells. The intranuclear proteasome abundance appeared to be inversely related to the rate of cell cycle progression, with restraint of the cell cycle being associated with an increase in the amount of proteasome subunits in the nucleus, suggesting that the nuclear proteasome content is dependent on the cell cycle. Furthermore, chromatin enrichment for proteomics (ChEP) analysis revealed enrichment of the proteasome in the chromatin fraction of quiescent cells and its apparent dissociation from chromatin in transformed cells. Our results thus suggest that translocation of the nuclear proteasome to chromatin may play an important role in control of the cell cycle and oncogenesis through regulation of chromatin-associated transcription factors.

| S-EPMC7118148 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data