GATA6 is a regulator of sinus node development and heart rhythm.
Proc Natl Acad Sci U S A
; 118(1)2021 01 05.
Article
in En
| MEDLINE
| ID: mdl-33443158
ABSTRACT
The sinus node (SAN) is the primary pacemaker of the human heart, and abnormalities in its structure or function cause sick sinus syndrome, the most common reason for electronic pacemaker implantation. Here we report that transcription factor GATA6, whose mutations in humans are linked to arrhythmia, is highly expressed in the SAN and its haploinsufficiency in mice results in hypoplastic SANs and rhythm abnormalities. Cell-specific deletion reveals a requirement for GATA6 in various SAN lineages. Mechanistically, GATA6 directly activates key regulators of the SAN genetic program in conduction and nonconduction cells, such as TBX3 and EDN1, respectively. The data identify GATA6 as an important regulator of the SAN and provide a molecular basis for understanding the conduction abnormalities associated with GATA6 mutations in humans. They also suggest that GATA6 may be a potential modifier of the cardiac pacemaker.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sinoatrial Node
/
GATA6 Transcription Factor
/
Heart Rate
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2021
Document type:
Article