Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcription factors that convert adult cell identity are differentially polycomb repressed.

ABSTRACT: Transcription factors that can convert adult cells of one type to another are usually discovered empirically by testing factors with a known developmental role in the target cell. Here we show that standard genomic methods (RNA-seq and ChIP-seq) can help identify these factors, as most are more strongly Polycomb repressed in the source cell and more highly expressed in the target cell. This criterion is an effective genome-wide screen that significantly enriches for factors that can transdifferentiate several mammalian cell types including neural stem cells, neurons, pancreatic islets, and hepatocytes. These results suggest that barriers between adult cell types, as depicted in Waddington's "epigenetic landscape", consist in part of differentially Polycomb-repressed transcription factors. This genomic model of cell identity helps rationalize a growing number of transdifferentiation protocols and may help facilitate the engineering of cell identity for regenerative medicine.

SUBMITTER: Davis FP

PROVIDER: S-EPMC3641127 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Transcription factors that convert adult cell identity are differentially polycomb repressed.

Davis Fred P FP Eddy Sean R SR

PloS one 20130501 5

Transcription factors that can convert adult cells of one type to another are usually discovered empirically by testing factors with a known developmental role in the target cell. Here we show that standard genomic methods (RNA-seq and ChIP-seq) can help identify these factors, as most are more strongly Polycomb repressed in the source cell and more highly expressed in the target cell. This criterion is an effective genome-wide screen that significantly enriches for factors that can transdiffere ...[more]

PMID: 23650565

Similar Datasets

Insulators target active genes to transcription factories and polycomb-repressed genes to polycomb bodies.

Project description:Polycomb bodies are foci of Polycomb proteins in which different Polycomb target genes are thought to co-localize in the nucleus, looping out from their chromosomal context. We have shown previously that insulators, not Polycomb response elements (PREs), mediate associations among Polycomb Group (PcG) targets to form Polycomb bodies. Here we use live imaging and 3C interactions to show that transgenes containing PREs and endogenous PcG-regulated genes are targeted by insulator proteins to different nuclear structures depending on their state of activity. When two genes are repressed, they co-localize in Polycomb bodies. When both are active, they are targeted to transcription factories in a fashion dependent on Trithorax and enhancer specificity as well as the insulator protein CTCF. In the absence of CTCF, assembly of Polycomb bodies is essentially reduced to those representing genomic clusters of Polycomb target genes. The critical role of Trithorax suggests that stable association with a specialized transcription factory underlies the cellular memory of the active state.

| S-EPMC3630138 | biostudies-literature

Repression of Abd-B by Polycomb is critical for cell identity maintenance in adult Drosophila testis.

Project description:Hox genes play a fundamental role in regulating animal development. However, less is known about their functions on homeostasis maintenance in adult stem cells. Here, we report that the repression of an important axial Hox gene, Abdominal-B (Abd-B), in cyst stem cells (CySCs) is essential for the homeostasis and cell identity maintenance in the adult Drosophila testis. Derepression of Abd-B in CySCs disrupts the proper self-renewal of both germline stem cells (GSCs) and CySCs, and leads to an excessive expansion of early stage somatic cells, which originate from both lineages. We further demonstrate that canonical Polycomb (Pc) and functional pathway of Polycomb group (PcG) proteins are responsible for maintaining the germline cell identity non-autonomously via repressing Abd-B in CySCs in the adult Drosophila testis.

| S-EPMC5506049 | biostudies-literature

SWI2/SNF2 chromatin remodeling ATPases overcome polycomb repression and control floral organ identity with the LEAFY and SEPALLATA3 transcription factors.

Project description:Patterning of the floral organs is exquisitely controlled and executed by four classes of homeotic regulators. Among these, the class B and class C floral homeotic regulators are of central importance as they specify the male and female reproductive organs. Inappropriate induction of the class B gene APETALA3 (AP3) and the class C gene AGAMOUS (AG) causes reduced reproductive fitness and is prevented by polycomb repression. At the onset of flower patterning, polycomb repression needs to be overcome to allow induction of AP3 and AG and formation of the reproductive organs. We show that the SWI2/SNF2 chromatin-remodeling ATPases SPLAYED (SYD) and BRAHMA (BRM) are redundantly required for flower patterning and for the activation of AP3 and AG. The SWI2/SNF2 ATPases are recruited to the regulatory regions of AP3 and AG during flower development and physically interact with two direct transcriptional activators of class B and class C gene expression, LEAFY (LFY) and SEPALLATA3 (SEP3). SYD and LFY association with the AP3 and AG regulatory loci peaks at the same time during flower patterning, and SYD binding to these loci is compromised in lfy and lfy sep3 mutants. This suggests a mechanism for SWI2/SNF2 ATPase recruitment to these loci at the right stage and in the correct cells. SYD and BRM act as trithorax proteins, and the requirement for SYD and BRM in flower patterning can be overcome by partial loss of polycomb activity in curly leaf (clf) mutants, implicating the SWI2/SNF2 chromatin remodelers in reversal of polycomb repression.

| S-EPMC3295252 | biostudies-literature

Polycomb complexes redundantly maintain epidermal stem cell identity during development.

Project description:Polycomb repressive complex 1 (PRC1) and PRC2 are critical epigenetic developmental regulators. PRC1 and PRC2 largely overlap in their genomic binding and cooperate to establish repressive chromatin domains demarcated by H2AK119ub and H3K27me3. However, the functional contribution of each complex to gene repression has been a subject of debate, and understanding of its physiological significance requires further studies. Here, using the developing murine epidermis as a paradigm, we uncovered a previously unappreciated functional redundancy between Polycomb complexes. Coablation of PRC1 and PRC2 in embryonic epidermal progenitors resulted in severe defects in epidermal stratification, a phenotype not observed in the single PRC1-null or PRC2-null epidermis. Molecular dissection indicated a loss of epidermal identity that was coupled to a strong derepression of nonlineage transcription factors, otherwise repressed by either PRC1 or PRC2 in the absence of its counterpart. Ectopic expression of subsets of PRC1/2-repressed nonepidermal transcription factors in wild-type epidermal stem cells was sufficient to suppress epidermal identity genes, highlighting the importance of functional redundancy between PRC1 and PRC2. Altogether, our studies show how PRC1 and PRC2 function as two independent counterparts, thereby providing a repressive safety net that protects and preserves lineage identity.

| S-EPMC7919412 | biostudies-literature

A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity.

Project description:Hundreds of transcription factors (TFs) are expressed in each cell type, but cell identity can be induced through the activity of just a small number of core TFs. Systematic identification of these core TFs for a wide variety of cell types is currently lacking and would establish a foundation for understanding the transcriptional control of cell identity in development, disease, and cell-based therapy. Here, we describe a computational approach that generates an atlas of candidate core TFs for a broad spectrum of human cells. The potential impact of the atlas was demonstrated via cellular reprogramming efforts where candidate core TFs proved capable of converting human fibroblasts to retinal pigment epithelial-like cells. These results suggest that candidate core TFs from the atlas will prove a useful starting point for studying transcriptional control of cell identity and reprogramming in many human cell types.

| S-EPMC4649293 | biostudies-literature

Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell identity.

Project description:A robust network of transcription factors and an open chromatin landscape are hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4 has been implicated in stem cell maintenance, but the relative contribution of Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression. In metastable ESCs, Brd4 independence can be achieved by increased expression of pluripotency transcription factors, including STAT3, Nanog or Klf4, so long as the DNA methylcytosine oxidases Tet1 and Tet2 are present. These data reveal that Brd4 is not essential for ESC self-renewal. Rather, the levels of pluripotency transcription factor abundance and Tet1/2 function determine the extent to which bromodomain recognition of protein acetylation contributes to the maintenance of gene expression and cell identity.

| S-EPMC5937285 | biostudies-literature

Polycomb-repressed genes have permissive enhancers that initiate reprogramming.

Project description:Key regulatory genes, suppressed by Polycomb and H3K27me3, become active during normal differentiation and induced reprogramming. Using the well-characterized enhancer/promoter pair of MYOD1 as a model, we have identified a critical role for enhancers in reprogramming. We observed an unexpected nucleosome-depleted region (NDR) at the H3K4me1-enriched enhancer at which transcriptional regulators initially bind, leading to subsequent changes in the chromatin at the cognate promoter. Exogenous Myod1 activates its own transcription by binding first at the enhancer, leading to an NDR and transcription-permissive chromatin at the associated MYOD1 promoter. Exogenous OCT4 also binds first to the permissive MYOD1 enhancer but has a different effect on the cognate promoter, where the monovalent H3K27me3 marks are converted to the bivalent state characteristic of stem cells. Genome-wide, a high percentage of Polycomb targets are associated with putative enhancers in permissive states, suggesting that they may provide a widespread avenue for the initiation of cell-fate reprogramming.

| S-EPMC3240866 | biostudies-literature

Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity.

Project description:Efficient transcriptional programming promises to open new frontiers in regenerative medicine. However, mechanisms by which programming factors transform cell fate are unknown, preventing more rational selection of factors to generate desirable cell types. Three transcription factors, Ngn2, Isl1 and Lhx3, were sufficient to program rapidly and efficiently spinal motor neuron identity when expressed in differentiating mouse embryonic stem cells. Replacement of Lhx3 by Phox2a led to specification of cranial, rather than spinal, motor neurons. Chromatin immunoprecipitation-sequencing analysis of Isl1, Lhx3 and Phox2a binding sites revealed that the two cell fates were programmed by the recruitment of Isl1-Lhx3 and Isl1-Phox2a complexes to distinct genomic locations characterized by a unique grammar of homeodomain binding motifs. Our findings suggest that synergistic interactions among transcription factors determine the specificity of their recruitment to cell type-specific binding sites and illustrate how a single transcription factor can be repurposed to program different cell types.

| S-EPMC3820498 | biostudies-literature

Master transcription factors and mediator establish super-enhancers at key cell identity genes.

Project description:Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). We report here that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. These domains, which we call super-enhancers, consist of clusters of enhancers that are densely occupied by the master regulators and Mediator. Super-enhancers differ from typical enhancers in size, transcription factor density and content, ability to activate transcription, and sensitivity to perturbation. Reduced levels of Oct4 or Mediator cause preferential loss of expression of super-enhancer-associated genes relative to other genes, suggesting how changes in gene expression programs might be accomplished during development. In other more differentiated cells, super-enhancers containing cell-type-specific master transcription factors are also found at genes that define cell identity. Super-enhancers thus play key roles in the control of mammalian cell identity.

| S-EPMC3653129 | biostudies-literature

Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2.

Project description:Polycomb proteins maintain cell identity by repressing the expression of developmental regulators specific for other cell types. Polycomb repressive complex-2 (PRC2) catalyzes trimethylation of histone H3 lysine-27 (H3K27me3). Although repressed, PRC2 targets are generally associated with the transcriptional initiation marker H3K4me3, but the significance of this remains unclear. Here, we identify a class of short RNAs, approximately 50-200 nucleotides in length, transcribed from the 5' end of polycomb target genes in primary T cells and embryonic stem cells. Short RNA transcription is associated with RNA polymerase II and H3K4me3, occurs in the absence of mRNA transcription, and is independent of polycomb activity. Short RNAs form stem-loop structures resembling PRC2 binding sites in Xist, interact with PRC2 through SUZ12, cause gene repression in cis, and are depleted from polycomb target genes activated during cell differentiation. We propose that short RNAs play a role in the association of PRC2 with its target genes.

| S-EPMC2886029 | 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