scholarly journals Genome-wide transcription factor localization and function in stem cells

StemBook ◽  
2008 ◽  
Author(s):  
Lim
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Genome Wide ◽  
And Function

scholarly journals Genome-Wide Identification of Targets and Function of Individual MicroRNAs in Mouse Embryonic Stem Cells

PLoS Genetics ◽  
2010 ◽  
Vol 6 (10) ◽  
pp. e1001163 ◽  
Author(s):  
Sophie A. Hanina ◽  
William Mifsud ◽  
Thomas A. Down ◽  
Katsuhiko Hayashi ◽  
Dónal O'Carroll ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Genome Wide ◽  
And Function

scholarly journals Genome-wide identification of long non-coding RNA targets of the tomato MADS box transcription factor RIN and function analysis

2018 ◽  
Vol 123 (3) ◽  
pp. 469-482 ◽  
Author(s):  
Tongtong Yu ◽  
David T W Tzeng ◽  
Ran Li ◽  
Jianye Chen ◽  
Silin Zhong ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Function Analysis ◽  
Mads Box ◽  
Non Coding Rna ◽  
Rna Targets ◽  
Genome Wide ◽  
And Function ◽  
Long Non Coding Rna

scholarly journals LncRNA HBL1 is required for genome-wide PRC2 occupancy and function in cardiogenesis from human pluripotent stem cells

Development ◽  
2021 ◽  
Author(s):  
Juli Liu ◽  
Sheng Liu ◽  
Lei Han ◽  
Yi Sheng ◽  
Yucheng Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Transcription ◽  
Pluripotent Stem Cells ◽  
Cardiac Development ◽  
Chromatin Modification ◽  
Human Pluripotent Stem Cells ◽  
Cardiac Differentiation ◽  
Genome Wide ◽  
And Function

Polycomb Repressive Complex 2 (PRC2) deposits H3K27me3 on chromatin to silence transcription. PRC2 broadly interacts with RNAs. Currently, the role of RNA- PRC2 interaction in human cardiogenesis remains elusive. Here, we found human-specific Heart Brake LncRNA 1 (HBL1) interacted with two PRC2 subunits, JARID2 and EED, in human pluripotent stem cells (hPSCs). Loss-of-JARID2, EED or HBL1 significantly enhanced cardiac differentiation from hPSCs. HBL1 depletion disrupted genome-wide PRC2 occupancy and H3K27me3 chromatin modification on essential cardiogenic genes, and broadly enhanced cardiogenic gene transcription in undifferentiated hPSCs and later-on differentiation. Additionally, ChIP-seq revealed reduced EED-occupancy on 62 overlapped cardiogenic genes in HBL1−/- and JARID2−/- hPSCs, indicating the epigenetic state of cardiogenic genes was determined by HBL1 and JARID2 at pluripotency stage. Furthermore, after cardiac development occurred, the cytosolic and nuclear fractions of HBL1 could crosstalk via a conserved “microRNA-1-JARID2” axis to modulate cardiogenic gene transcription. Overall, our findings delineate the indispensable role of HBL1 in guiding PRC2 function during early human cardiogenesis, and expand the mechanistic scope of lncRNA(s) that cytosolic and nuclear portions of HBL1 could coordinate to orchestrate human cardiogenesis.

scholarly journals Epigenetic inactivation of oncogenic brachyury (TBXT) by H3K27 histone demethylase controls chordoma cell survival

2018 ◽  
Author(s):  
Lucia Cottone ◽  
Edward S Hookway ◽  
Adam Cribbs ◽  
Graham Wells ◽  
Patrick Lombard ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Fate ◽  
Control Mechanisms ◽  
Rare Tumour ◽  
Mesoderm Development ◽  
Survival Pathways ◽  
Genome Wide ◽  
Notochord Cell ◽  
Oncogenic Driver ◽  
And Function

AbstractThe expression of the transcription factorbrachyury(TBXT) is normally restricted to embryonic development and its silencing after mesoderm development is epigenetically regulated. In chordoma, a rare tumour of notochordal differentiation, TBXT acts as a putative oncogene, and we hypothesised that its expression could be controlled through epigenetic inhibition. Screening of five chordoma cell lines revealed that only inhibitors of the histone 3 lysine 27 demethylases KDM6A (UTX) and KDM6B (Jmjd3) reduceTBXTexpression and lead to cell death, findings validated in primary patient-derived culture systems. Pharmacological inhibition of KDM6 demethylases leads to genome-wide increases in repressive H3K27me3 marks, accompanied by significantly reduced TBXT expression, an effect that is phenocopied by the dual genetic inactivation ofKDM6A/Busing CRISPR/Cas9. Transcriptional profiles in response to a novel KDM6A/B inhibitor, KDOBA67, revealed downregulation of critical genes and transcription factor networks for chordoma survival pathways, whereas upregulated pathways were dominated by stress, cell cycle and pro-apoptotic response pathways.This study supports previous data showing that the function of TBXT is essential for maintaining notochord cell fate and function and provides further evidence that TBXT is an oncogenic driver in chordoma. Moreover, the data suggest that TBXT can potentially be targeted therapeutically by modulating epigenetic control mechanisms such as H3K27 demethylases.

scholarly journals Homotypic cooperativity and collective binding are determinants of bHLH specificity and function

2019 ◽  
Vol 116 (32) ◽  
pp. 16143-16152 ◽  
Author(s):  
Christian A. Shively ◽  
Jiayue Liu ◽  
Xuhua Chen ◽  
Kaiser Loell ◽  
Robi D. Mitra
Keyword(s):  
Transcription Factor ◽  
Dna Sequences ◽  
Dna Binding Proteins ◽  
Eukaryotic Cells ◽  
Sequence Information ◽  
Genome Wide ◽  
Important Open Problem ◽  
And Function

Eukaryotic cells express transcription factor (TF) paralogues that bind to nearly identical DNA sequences in vitro but bind at different genomic loci and perform different functions in vivo. Predicting how 2 paralogous TFs bind in vivo using DNA sequence alone is an important open problem. Here, we analyzed 2 yeast bHLH TFs, Cbf1p and Tye7p, which have highly similar binding preferences in vitro, yet bind at almost completely nonoverlapping target loci in vivo. We dissected the determinants of specificity for these 2 proteins by making a number of chimeric TFs in which we swapped different domains of Cbf1p and Tye7p and determined the effects on in vivo binding and cellular function. From these experiments, we learned that the Cbf1p dimer achieves its specificity by binding cooperatively with other Cbf1p dimers bound nearby. In contrast, we found that Tye7p achieves its specificity by binding cooperatively with 3 other DNA-binding proteins, Gcr1p, Gcr2p, and Rap1p. Remarkably, most promoters (63%) that are bound by Tye7p do not contain a consensus Tye7p binding site. Using this information, we were able to build simple models to accurately discriminate bound and unbound genomic loci for both Cbf1p and Tye7p. We then successfully reprogrammed the human bHLH NPAS2 to bind Cbf1p in vivo targets and a Tye7p target intergenic region to be bound by Cbf1p. These results demonstrate that the genome-wide binding targets of paralogous TFs can be discriminated using sequence information, and provide lessons about TF specificity that can be applied across the phylogenetic tree.

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