scholarly journals Histone demethylome map reveals combinatorial gene regulatory functions in embryonic stem cells

2020 ◽  
Author(s):  
Yogesh Kumar ◽  
Pratibha Tripathi ◽  
Majid Mehravar ◽  
Michael J. Bullen ◽  
Varun K. Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Gene Regulation ◽  
Embryonic Stem Cells ◽  
Regulatory Network ◽  
Regulatory Networks ◽  
Target Gene ◽  
Embryonic Stem ◽  
Epigenetic Regulators ◽  
Regulatory Functions

SUMMARYEpigenetic regulators and transcription factors establish distinct regulatory networks for gene regulation to maintain the embryonic stem cells (ESC) state. Although much has been learned regarding individual epigenetic regulators, their combinatorial functions remain elusive. Here, we report combinatorial functions of histone demethylases (HDMs) in gene regulation of mouse ESCs that are currently unknown. We generated a histone demethylome (HDMome) map of 20 well-characterized HDMs based on their genome-wide binding. This revealed co-occupancy of HDMs in different combinations; predominantly, KDM1A-KDM4B-KDM6A and JARID2-KDM4A-KDM4C-KDM5B co-occupy at enhancers and promoters, respectively. Comprehensive mechanistic studies uncover that KDM1A-KDM6A combinatorially modulates P300/H3K27ac, H3K4me1, H3K4me2 deposition and OCT4 recruitment that eventually directs the OCT4/CORE regulatory network for target gene expression; while co-operative actions of JARID2-KDM4A-KDM4C-KDM5B control H2AK119ub1 and bivalent marks of polycomb-repressive complexes that facilitates the PRC regulatory network for target gene repression. Thus, combinatorial functions of HDMs impact gene expression programs to maintain the ESC state.

scholarly journals Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (1) ◽  
pp. e4268 ◽  
Author(s):  
Marcela Guzman-Ayala ◽  
Kian Leong Lee ◽  
Konstantinos J. Mavrakis ◽  
Paraskevi Goggolidou ◽  
Dominic P. Norris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Target Gene ◽  
Embryonic Stem ◽  
Target Gene Expression

scholarly journals Correction: Graded Smad2/3 Activation Is Converted Directly into Levels of Target Gene Expression in Embryonic Stem Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (2) ◽  
Author(s):  
Marcela Guzman-Ayala ◽  
Kian Leong Lee ◽  
Konstantinos J. Mavrakis ◽  
Paraskevi Goggolidou ◽  
Dominic P. Norris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Target Gene ◽  
Embryonic Stem ◽  
Target Gene Expression

scholarly journals Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development

2017 ◽  
Vol 114 (52) ◽  
pp. E11180-E11189 ◽  
Author(s):  
Kesavan Meganathan ◽  
Emily M. A. Lewis ◽  
Paul Gontarz ◽  
Shaopeng Liu ◽  
Edouard G. Stanley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Chromatin Remodeling ◽  
Human Embryonic Stem Cells ◽  
Regulatory Networks ◽  
Embryonic Stem ◽  
Molecular Networks ◽  
Cortical Interneurons

Cortical interneurons (cINs) modulate excitatory neuronal activity by providing local inhibition. During fetal development, several cIN subtypes derive from the medial ganglionic eminence (MGE), a transient ventral telencephalic structure. While altered cIN development contributes to neurodevelopmental disorders, the inaccessibility of human fetal brain tissue during development has hampered efforts to define molecular networks controlling this process. Here, we modified protocols for directed differentiation of human embryonic stem cells, obtaining efficient, accelerated production of MGE-like progenitors and MGE-derived cIN subtypes with the expected electrophysiological properties. We defined transcriptome changes accompanying this process and integrated these data with direct transcriptional targets of NKX2-1, a transcription factor controlling MGE specification. This analysis defined NKX2-1–associated genes with enriched expression during MGE specification and cIN differentiation, including known and previously unreported transcription factor targets with likely roles in MGE specification, and other target classes regulating cIN migration and function. NKX2-1–associated peaks were enriched for consensus binding motifs for NKX2-1, LHX, and SOX transcription factors, suggesting roles in coregulating MGE gene expression. Among the NKX2-1 direct target genes with cIN-enriched expression was CHD2, which encodes a chromatin remodeling protein mutated to cause human epilepsies. Accordingly, CHD2 deficiency impaired cIN specification and altered later electrophysiological function, while CHD2 coassociated with NKX2-1 at cis-regulatory elements and was required for their transactivation by NKX2-1 in MGE-like progenitors. This analysis identified several aspects of gene-regulatory networks underlying human MGE specification and suggested mechanisms by which NKX2-1 acts with chromatin remodeling activities to regulate gene expression programs underlying cIN development.

Ethanol alters cell cycle gene expression in human embryonic stem cells

2016 ◽  
Vol 01 (03) ◽  
pp. 201-208 ◽  
Author(s):  
Malini Krishnamoorthy ◽  
Brian Gerwe ◽  
Jamie Heimburg-Molinaro ◽  
Rachel Nash ◽  
Jagan Arumugham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Cycle Gene ◽  
Cell Cycle Gene Expression

scholarly journals The Trends in Global Gene Expression in Mouse Embryonic Stem Cells During Spaceflight

2019 ◽  
Vol 10 ◽  
Author(s):  
Lili An ◽  
Yanming Li ◽  
Yingjun Fan ◽  
Ning He ◽  
Fanlei Ran ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Global Gene Expression ◽  
Mouse Embryonic Stem Cells

3076 – FINE-TUNING GENE EXPRESSION BY CRISPRA IN MOUSE EMBRYONIC STEM CELLS FOR SPECIFIC TISSUE INDUCTION

2020 ◽  
Vol 88 ◽  
pp. S62
Author(s):  
Luis Galán Palma ◽  
Roshana Thambyrajah ◽  
Antonella Fidanza ◽  
Lesley Forrester ◽  
Pablo Menéndez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cells ◽  
Fine Tuning ◽  
Specific Tissue

Positive regulators of the lineage-specific transcription factor GATA-1 in differentiating erythroid cells

1994 ◽  
Vol 14 (5) ◽  
pp. 3108-3114
Author(s):  
M H Baron ◽  
S M Farrington
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Transcription Factor ◽  
Embryonic Stem Cells ◽  
Cultured Cells ◽  
Globin Gene ◽  
Embryonic Stem ◽  
Targeted Mutagenesis ◽  
Erythroid Cell ◽  
Erythroid Cells

The zinc finger transcription factor GATA-1 is a major regulator of gene expression in erythroid, megakaryocyte, and mast cell lineages. GATA-1 binds to WGATAR consensus motifs in the regulatory regions of virtually all erythroid cell-specific genes. Analyses with cultured cells and cell-free systems have provided strong evidence that GATA-1 is involved in control of globin gene expression during erythroid differentiation. Targeted mutagenesis of the GATA-1 gene in embryonic stem cells has demonstrated its requirement in normal erythroid development. Efficient rescue of the defect requires an intact GATA element in the distal promoter, suggesting autoregulatory control of GATA-1 transcription. To examine whether GATA-1 expression involves additional regulatory factors or is maintained entirely by an autoregulatory loop, we have used a transient heterokaryon system to test the ability of erythroid factors to activate the GATA-1 gene in nonerythroid nuclei. We show here that proerythroblasts and mature erythroid cells contain a diffusible activity (TAG) capable of transcriptional activation of GATA-1 and that this activity decreases during the terminal differentiation of erythroid cells. Nuclei from GATA-1- mutant embryonic stem cells can still be reprogrammed to express their globin genes in erythroid heterokaryons, indicating that de novo induction of GATA-1 is not required for globin gene activation following cell fusion.

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