Chromatin regulators (CRs) are crucial for connecting the chromatin level and transcriptome level by modulating chromatin structures, establishing, and maintaining epigenetic modifications. We present a systematic method to identify MOdulation of transcriptional regulation via CHromatin Activity (MOCHA) from gene expression data and demonstrate its advantage in associating CRs to their chromatin localization and understand CRs' function. We first re-construct the CRs modulation network by integrating the correlation and conditional correlation concepts. Then we quantify the chromatin activity as hidden variable in network by integrating the upstream and downstream information. We applied MOCHA to systematically explore the interplay of CRs, TFs, and target genes in mouse embryonic stem cells (ESC). As a result, MOCHA identified 420 chromatin regulators with modulation preference, including Pou5f1 and Eed. We found that BAF complex, NuRD complex, and polycomb-group proteins, regulate the delicate balance between pluripotency and differentiation by modulating key TFs including Klf4, Tcf3, and Max; NuRD complex members Mbd3 and Hdac1 may modulate Klf4 to achieve its dual functional roles in pluripotent and differentiation stages;Imprinted gene H19 and Igf2 are modulated by DNA methylation, histone acetylation, and insulator CTCF. Finally, we analyzed CR's combinational modulation pattern by constructing a CR-CR interaction network.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780077 | PMC |
| http://dx.doi.org/10.1038/srep22656 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A scATAC-seq atlas of stasis zone in rat skin burn injury wound process.
Front Cell Dev Biol
January 2025
Department of Burn Surgery, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
Burn injuries often leave behind a "stasis zone", a region of tissue critically important for determining both the severity of the injury and the potential for recovery. To understand the intricate cellular and epigenetic changes occurring within this critical zone, we utilized single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to profile over 31,500 cells from both healthy rat skin and the stasis zone at nine different time points after a burn injury. This comprehensive approach revealed 26 distinct cell types and the dynamic shifts in the proportions of these cell types over time.
View Article and Find Full Text PDFGenetic predisposition to Behcet's disease mediated by a IL10RA enhancer polymorphism.
Heliyon
January 2025
The First Affiliated Hospital of Chongqing Medical University, Chongqing Branch (Municipality Division) of National Clinical Research Center for Ocular Diseases, Chongqing, PR China.
Background: Several studies suggested the genetic association between IL10RA variants and susceptibility to Behcet's disease (BD). However, the precise mechanism of the association is still unknown. The purpose of this study was to investigate the mechanism underlying the genetic associations between IL10RA polymorphisms and the risk of BD.
View Article and Find Full Text PDFStochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition.
J Exp Clin Cancer Res
January 2025
Department of Cancer Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Background: Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.
Methods: In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level.
Therapeutic potential of targeting the IRF2/POSTN/Notch1 axis in nucleus pulposus cells for intervertebral disc degeneration.
J Neuroinflammation
January 2025
Lanzhou University Second Hospital, 82 Cui-Ying-Men, Lanzhou, 730030, PR China.
Background: Intervertebral disc degeneration (IDD) is a leading cause of low back pain, often linked to inflammation and pyroptosis in nucleus pulposus (NP) cells. The role of Periostin (POSTN) in IDD remains unclear.
Objective: This study aims to investigate the influence of POSTN on pyroptosis and NLRP3 inflammasome activation in NP cells during IDD.
Improved ChIP Sequencing for H3K27ac Profiling and Super-Enhancer Analysis Assisted by Fluorescence-Activated Sorting of Formalin-Fixed Paraffin-Embedded Tissues.
Biol Proced Online
January 2025
Department of Laboratory Medicine, West China Hospital of Sichuan University, Chengdu, 610041, China.
Archived clinical formalin-fixed paraffin-embedded tissue (FFPE) is valuable for the study of tumor epigenetics. Although protocol of chromatin immunoprecipitation coupled with next generation sequencing (NGS) (ChIP-seq) using FFPE samples has been established, removal of interference signals from non-target cell components in the samples is still needed. In this study, the protocol of ChIP-seq with purified cells from FFPE lymphoid tissue of nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI) after fluorescence-activated cell sorting (FACS) was established and optimized.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!