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NKX2-5 inhibits HCN4. 7 / 8
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"In the present study, Nkx2.5 silencing increased HCN4 mRNA and protein expression levels in HL-1 cells, which may generate abnormal automaticity and pacemaker activity in the atrium in vivo."
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"Nkx2-5 acts to repress Hcn4 and Tbx3, and is required to establish the SAN-atrial boundary [XREF_BIBR, XREF_BIBR]."
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"NKX2.5 , a main transcriptional factor of working myocardium , upregulates the expression of downstream genes including SCN5A but represses the expression of HCN4 ( Barbuti and Robinson , 2015 ; Vedantham , 2015 ) ."
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"The non-pacemaker-specific, ventricular-like transcription factor Nkx2.5, by contrast, suppresses HCN4 as well as TBX3 [58] and upregulates the atrial marker Cx40 [59]."
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"Evidence from knockout mouse studies indicates that Nkx2.5 is a transcriptional repressor of Hcn4."
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"SHOX2 inhibits NKX2.5 expression and activates a pacemaker genetic pathway that results in up-regulation of the GATA6 and TBX3 transcription factors, and HCN4 channel."
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"In working atrial myocardium that lacks the repressive effects of Shox2, Nkx2.5 activates expression of chamber specific genes (Cx40/Cx43/ANF) and represses SAN specific genes (Tbx3 and HCN4) to prevent ectopic pacemaker formation."
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