Accession

PRJCA011579

Title

Enhancer architecture-dependent multilayered transcriptional regulation orchestrates RA signaling-induced early lineage differentiation of ESCs

Relevance

Medical

Data types

Raw sequence reads

Organisms

Mus musculus

Description

Signaling pathway driven target gene transcriptions are critical for fate determination of embryonic stem cells (ESC), but enhancer architecture-dependent transcriptional regulation remains largely unclear in this process. Here, we described a complex enhancer architecture-dependent multilayered transcriptional regulation that orchestrates retinoic acid (RA) signal-induced early differentiation of ESC. Specifically, we identified Hoxa1 and lncRNA Halr1 as the direct downstream target genes of RA signal. Chromosome conformation capture based screens show that increased enhancer interactions promoted by RA signal are essential for Hoxa1 and Halr1 expressions during early ESC differentiation. Furthermore, we find that HOXA1 promotes Halr1 expression through direct binding to enhancers; conversely, absence of Halr1 RNA enhances interaction between Hoxa1 chromatin and multiple enhancers, but weakens interaction with HoxA cluster internal chromatin, thereby promoting RA signal-induced Hoxa1 overactivation and early differentiation of ESC. These results indicate that Halr1 binds to chromatin not only acts as a brake to orchestrate interaction between enhancers and Hoxa1 chromatin, but also acts as a binder to maintain chromatin interaction within HoxA cluster. In summary, these findings reveal a complex multilayered transcriptional regulation involving the synergistic regulation of enhancer, transcription factor and lncRNA, and that increases our understanding of the intrinsic molecular mechanisms of RA signal-induced ESC differentiation.

Sample scope

Multiisolate

Release date

2022-08-31

Publication

PubMed ID	Article title	Journal name	DOI	Year
	Enhancer architecture-dependent multilayered transcriptional regulation orchestrates RA signaling-induced early lineage differentiation of ESCs	Nucleic Acids Research	10.1093/nar/gkab1001	2021

Grants

Agency	program	Grant ID	Grant title
Ministry of Science and Technology of the People's Republic of China (MOST)	National Key Technologies R&D Program	2017YFA0102600

Accessions in other database

Accession	Database name
SRP311002	NCBI

Submitter

Wenbin Wang (sciencedb@gibh.ac.cn)

Organization

Nankai University

Submission date

2022-08-31

Project Data

Resource name	Description
BioSample (29) show	-
SAMC867596	Halr1-KO-RA-1d-Capture-C
SAMC867595	WT-RA-1d-Capture-C
SAMC867594	WT-RA-0d-Capture-C
SAMC867593	DKO(Hoxa1-Halr1)-RA-1d-RNA-seq-Rep3
SAMC867592	DKO(Hoxa1-Halr1)-RA-1d-RNA-seq-Rep2
SAMC867591	DKO(Hoxa1-Halr1)-RA-1d-RNA-seq-Rep1
SAMC867590	Hoxa1-KO-RA-1d-RNA-seq-Rep3
SAMC867589	Hoxa1-KO-RA-1d-RNA-seq-Rep2
SAMC867588	Hoxa1-KO-RA-1d-RNA-seq-Rep1
SAMC867587	Hoxa1-WT-RA-1d-RNA-seq-Rep3
SAMC867586	Hoxa1-WT-RA-1d-RNA-seq-Rep2
SAMC867585	Hoxa1-WT-RA-1d-RNA-seq-Rep1
SAMC867584	Halr1-KO-RA-1d-RNA-seq-Rep3
SAMC867583	Halr1-KO-RA-1d-RNA-seq-Rep2
SAMC867582	Halr1-KO-RA-1d-RNA-seq-Rep1
SAMC867581	Halr1-WT-RA-1d-RNA-seq-Rep3
SAMC867580	Halr1-WT-RA-1d-RNA-seq-Rep2
SAMC867579	Halr1-WT-RA-1d-RNA-seq-Rep1
SAMC867578	En1-2-3-KO-RA-1d-RNA-seq-Rep2
SAMC867577	En1-2-3-KO-RA-1d-RNA-seq-Rep1
SAMC867576	En2-KO-RA-1d-RNA-seq-Rep2
SAMC867575	En2-KO-RA-1d-RNA-seq-Rep1
SAMC867574	En1-KO-RA-1d-RNA-seq-Rep2
SAMC867573	En1-KO-RA-1d-RNA-seq-Rep1
SAMC867572	En-WT-RA-1d-RNA-seq-Rep2
SAMC867571	En-WT-RA-1d-RNA-seq-Rep1
SAMC867570	WT-RA-0d-RNA-seq-Rep3
SAMC867569	WT-RA-0d-RNA-seq-Rep2
SAMC867568	WT-RA-0d-RNA-seq-Rep1
GSA (1)	-
CRA008026	Enhancer architecture-dependent multilayered transcriptional regulation orchestrates RA signaling-induced early lineage differentiation of ESCs