Regulation of Murine Cytochrome c Oxidase Vb Gene Expression during Myogenesis: YY-1 AND HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN D-LIKE PROTEIN (JKTBP1) RECIPROCALLY REGULATE TRANSCRIPTION ACTIVITY BY PHYSICAL INTERACTION WITH THE BERF-1/ZBP-89 FACTOR

Ettickan Boopathi,Nibedita Lenka,Subbuswamy K Prabu,Ji-Kang Fang,Frank Wilkinson,Michael Atchison,Agata Giallongo,Narayan G Avadhani

doi:10.1074/jbc.m403160200

Abstract

A transcription suppressor element (sequence -481 to -320) containing a G-rich motif (designated GTG) and a newly identified CAT-rich motif (designated CATR) was previously shown to modulate expression of the mouse cytochrome c oxidase Vb gene during myogenesis. Here, we show that the GTG element is critical for transcription activation in both undifferentiated and differentiated myocytes. Mutations of the CATR motif abolished transcription repression in myoblasts while limiting transcription activation in differentiated myotubes, suggesting contrasting functional attributes of this DNA motif at different stages of myogenesis. Results show that the activity of the transcription suppressor motif is modulated by an orchestrated interplay between ubiquitous transcription factors: ZBP-89, YY-1, and a member of the heterogeneous nuclear ribonucleoprotein D-like protein (also known as JKTBP1) family. In undifferentiated muscle cells, GTG motif-bound ZBP-89 physically and functionally interacted with CATR motif-bound YY-1 to mediate transcription repression. In differentiated myotubes, heterogeneous nuclear ribonucleoprotein D-like protein/JKTBP1 bound to the CATR motif exclusive of YY-1 and interacted with ZBP-89 in attenuating repressor activity, leading to transcription activation. Our results show a novel mechanism of protein factor switching in transcription regulation of the cytochrome c oxidase Vb gene during myogenesis.

Highlights

A transcription suppressor element containing a G-rich motif and a newly identified CAT-rich motif was previously shown to modulate expression of the mouse cytochrome c oxidase Vb gene during myogenesis
A common emerging theme among these and other mitochondrially destined oxidative phosphorylation genes is that a majority of them are positively regulated by transcription factors NRF1 and NRF2, the latter known as GA-binding protein [13], some are modulated by more general factors such as YY-1 and Sp1 (14 –16)
These results suggest that the CATR site may augment the suppressor activity in undifferentiated myocytes, whereas it may have an activator function in differentiated myotubes

Summary

Introduction

A transcription suppressor element (sequence ؊481 to ؊320) containing a G-rich motif (designated GTG) and a newly identified CAT-rich motif (designated CATR) was previously shown to modulate expression of the mouse cytochrome c oxidase Vb gene during myogenesis. Results show that the activity of the transcription suppressor motif is modulated by an orchestrated interplay between ubiquitous transcription factors: ZBP-89, YY-1, and a member of the heterogeneous nuclear ribonucleoprotein D-like protein ( known as JKTBP1) family. A common emerging theme among these and other mitochondrially destined oxidative phosphorylation genes is that a majority of them are positively regulated by transcription factors NRF1 and NRF2, the latter known as GA-binding protein [13], some are modulated by more general factors such as YY-1 and Sp1 (14 –16). Expression of the COX Vb gene is subject to regulation by NRF1 and NRF2, which bind to the immediate upstream regions of the promoter [20]

Methods

Results

Conclusion