AI Article Synopsis
- Brd4 is a critical factor in controlling gene expression during cell differentiation and development, particularly in adipogenesis (fat cell formation) and myogenesis (muscle cell formation).
- Brd4 works with key transcription factors and modifying enzymes at active enhancers to facilitate the recruitment of transcription machinery, essential for the production of enhancer RNAs and cell identity genes.
- Although Brd4 is crucial during differentiation, it is not required for the maintenance of cell identity genes in already differentiated cells.
Article Abstract
The epigenomic reader Brd4 is an important drug target for cancers. However, its role in cell differentiation and animal development remains largely unclear. Using two conditional knockout mouse strains and derived cells, we demonstrate that Brd4 controls cell identity gene induction and is essential for adipogenesis and myogenesis. Brd4 co-localizes with lineage-determining transcription factors (LDTFs) on active enhancers during differentiation. LDTFs coordinate with H3K4 mono-methyltransferases MLL3/MLL4 (KMT2C/KMT2D) and H3K27 acetyltransferases CBP/p300 to recruit Brd4 to enhancers activated during differentiation. Brd4 deletion prevents the enrichment of Mediator and RNA polymerase II transcription machinery, but not that of LDTFs, MLL3/MLL4-mediated H3K4me1, and CBP/p300-mediated H3K27ac, on enhancers. Consequently, Brd4 deletion prevents enhancer RNA production, cell identity gene induction and cell differentiation. Interestingly, Brd4 is dispensable for maintaining cell identity genes in differentiated cells. These findings identify Brd4 as an enhancer epigenomic reader that links active enhancers with cell identity gene induction in differentiation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738375 | PMC |
| http://dx.doi.org/10.1038/s41467-017-02403-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Human brain aging is associated with dysregulation of cell type epigenetic identity.
Geroscience
December 2024
Department of Ecology, Evolution, and Marine Biology, Department of Molecular, Cellular, and Cell Biology, Neuroscience Research Institute, University of California, Santa Barbara, CA, 93106, USA.
Significant links between aging and DNA methylation are emerging from recent studies. On the one hand, DNA methylation undergoes changes with age, a process termed as epigenetic drift. On the other hand, DNA methylation serves as a readily accessible and accurate biomarker for aging.
View Article and Find Full Text PDFAlternative splicing controls pan-neuronal homeobox gene expression.
Genes Dev
December 2024
Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10025, USA.
The pan-neuronally expressed and phylogenetically conserved CUT homeobox gene orchestrates pan-neuronal gene expression throughout the nervous system of As in many other species, including humans, is encoded by a complex locus that also codes for a Golgi-localized protein, called CASP (Cux1 alternatively spliced product) in humans and CONE-1 ("CASP of nematodes") in How gene expression from this complex locus is controlled-and, in , directed to all cells of the nervous system-has not been investigated. We show here that pan-neuronal expression of CEH-44/CUX is controlled by a pan-neuronal RNA splicing factor, UNC-75, the homolog of vertebrate CELF proteins. During embryogenesis, the locus exclusively produces the Golgi-localized CONE-1/CASP protein in all tissues, but upon the onset of postmitotic terminal differentiation of neurons, UNC-75/CELF induces the production of the alternative CEH-44/CUX CUT homeobox gene-encoding transcript exclusively in the nervous system.
View Article and Find Full Text PDFSingle-cell analysis of bidirectional reprogramming between early embryonic states identify mechanisms of differential lineage plasticities in mice.
Dev Cell
December 2024
Developmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Biochemistry, Cell and Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA. Electronic address:
Two distinct lineages, pluripotent epiblast (EPI) and primitive (extra-embryonic) endoderm (PrE), arise from common inner cell mass (ICM) progenitors in mammalian embryos. To study how these sister identities are forged, we leveraged mouse embryonic stem (ES) cells and extra-embryonic endoderm (XEN) stem cells-in vitro counterparts of the EPI and PrE. Bidirectional reprogramming between ES and XEN coupled with single-cell RNA and ATAC-seq analyses showed distinct rates, efficiencies, and trajectories of state conversions, identifying drivers and roadblocks of reciprocal conversions.
View Article and Find Full Text PDFMore Than Body Parts: A New Ethos of Anatomy Education.
Acad Med
October 2024
T.H. Champney is professor, Department of Cell Biology, University of Miami Miller School of Medicine, Miami, Florida; ORCID: https://orcid.org/0000-0002-0507-1663.
A new ethos of anatomy education goes beyond the learning of body parts in the traditional curriculum. In the traditional curriculum, the focus of only providing information on the structure of the human body left certain learning opportunities overlooked, marginalized, or dismissed as irrelevant; thus, opportunities to foster and shape professional attributes in health care learners were lost. Furthermore, changes in curricula structures and reductions in anatomy teaching hours have necessitated a transformation in how anatomy education is perceived and delivered.
View Article and Find Full Text PDFRapid whole genome characterization of antimicrobial-resistant pathogens using long-read sequencing to identify potential healthcare transmission.
Infect Control Hosp Epidemiol
December 2024
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Objective: Whole genome sequencing (WGS) can help identify transmission of pathogens causing healthcare-associated infections (HAIs). However, the current gold standard of short-read, Illumina-based WGS is labor and time intensive. Given recent improvements in long-read Oxford Nanopore Technologies (ONT) sequencing, we sought to establish a low resource approach providing accurate WGS-pathogen comparison within a time frame allowing for infection prevention and control (IPC) interventions.
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!