Myh7b/miR-499 gene expression is transcriptionally regulated by MRFs and Eos.

Abstract:

:The sarcomeric myosin gene, Myh7b, encodes an intronic microRNA, miR-499, which regulates cardiac and skeletal muscle biology, yet little is known about its transcriptional regulation. To identify the transcription factors involved in regulating Myh7b/miR-499 gene expression, we have mapped the transcriptional start sites and identified an upstream 6.2 kb region of the mouse Myh7b gene whose activity mimics the expression pattern of the endogenous Myh7b gene both in vitro and in vivo. Through promoter deletion analysis, we have mapped a distal E-box element and a proximal Ikaros site that are essential for Myh7b promoter activity in muscle cells. We show that the myogenic regulatory factors, MyoD, Myf5 and Myogenin, bind to the E-box, while a lymphoid transcription factor, Ikaros 4 (Eos), binds to the Ikaros motif. Further, we show that through physical interaction, MyoD and Eos form an active transcriptional complex on the chromatin to regulate the expression of the endogenous Myh7b/miR-499 gene in muscle cells. We also provide the first evidence that Eos can regulate expression of additional myosin genes (Myosin 1 and β-Myosin) via the miR-499/Sox6 pathway. Therefore, our results indicate a novel role for Eos in the regulation of the myofiber gene program.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Yeung F,Chung E,Guess MG,Bell ML,Leinwand LA

doi

10.1093/nar/gks466

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

7303-18

issue

15

eissn

0305-1048

issn

1362-4962

pii

gks466

journal_volume

40

pub_type

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