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Two upstream enhancers collaborate to regulate the spatial patterning and timing of MyoD transcription during mouse development.
Dev Dyn. 2001 Jul; 221(3):274-88.DD

Abstract

MyoD is a member of the basic-helix-loop-helix (bHLH) transcription factor family, which regulates muscle determination and differentiation in vertebrates. While it is now well established that the MyoD gene is regulated by Sonic hedgehog, Wnts, and other signals, it is not known how MyoD transcription is initiated and maintained in response to these signals. We have investigated the cis control of MyoD expression to identify and characterize the DNA targets that mediate MyoD transcription in embryos. By monitoring lacZ reporter gene expression in transgenic mice, we show that regulatory information contained in 24 kb of human MyoD 5' flanking sequence is sufficient to accurately control MyoD expression in embryos. Previous studies have identified two muscle-specific regulatory regions upstream of MyoD, a 4-kb region centered at -20 kb (designated fragment 3) that contains a highly conserved 258-bp core enhancer sequence, and a more proximal enhancer at -5 kb, termed the distal regulatory region (DRR), that heretofore has been identified only in mice. Here, we identify DRR-related sequences in humans and show that DRR function is conserved in humans and mice. In addition, transcriptional activity of MyoD 5' flanking sequences in somites and limb buds is largely a composite of the individual specificities of the two enhancers. Deletion of fragment 3 resulted in dramatic but temporary expression defects in the hypaxial myotome and limb buds, suggesting that this regulatory region is essential for proper temporal and spatial patterning of MyoD expression. These data indicate that regulatory sequences in fragment 3 are important targets of embryonic signaling required for the initiation of MyoD expression.

Authors+Show Affiliations

Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6058, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11458388

Citation

Chen, J C., et al. "Two Upstream Enhancers Collaborate to Regulate the Spatial Patterning and Timing of MyoD Transcription During Mouse Development." Developmental Dynamics : an Official Publication of the American Association of Anatomists, vol. 221, no. 3, 2001, pp. 274-88.
Chen JC, Love CM, Goldhamer DJ. Two upstream enhancers collaborate to regulate the spatial patterning and timing of MyoD transcription during mouse development. Dev Dyn. 2001;221(3):274-88.
Chen, J. C., Love, C. M., & Goldhamer, D. J. (2001). Two upstream enhancers collaborate to regulate the spatial patterning and timing of MyoD transcription during mouse development. Developmental Dynamics : an Official Publication of the American Association of Anatomists, 221(3), 274-88.
Chen JC, Love CM, Goldhamer DJ. Two Upstream Enhancers Collaborate to Regulate the Spatial Patterning and Timing of MyoD Transcription During Mouse Development. Dev Dyn. 2001;221(3):274-88. PubMed PMID: 11458388.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two upstream enhancers collaborate to regulate the spatial patterning and timing of MyoD transcription during mouse development. AU - Chen,J C, AU - Love,C M, AU - Goldhamer,D J, PY - 2001/7/18/pubmed PY - 2001/10/12/medline PY - 2001/7/18/entrez SP - 274 EP - 88 JF - Developmental dynamics : an official publication of the American Association of Anatomists JO - Dev Dyn VL - 221 IS - 3 N2 - MyoD is a member of the basic-helix-loop-helix (bHLH) transcription factor family, which regulates muscle determination and differentiation in vertebrates. While it is now well established that the MyoD gene is regulated by Sonic hedgehog, Wnts, and other signals, it is not known how MyoD transcription is initiated and maintained in response to these signals. We have investigated the cis control of MyoD expression to identify and characterize the DNA targets that mediate MyoD transcription in embryos. By monitoring lacZ reporter gene expression in transgenic mice, we show that regulatory information contained in 24 kb of human MyoD 5' flanking sequence is sufficient to accurately control MyoD expression in embryos. Previous studies have identified two muscle-specific regulatory regions upstream of MyoD, a 4-kb region centered at -20 kb (designated fragment 3) that contains a highly conserved 258-bp core enhancer sequence, and a more proximal enhancer at -5 kb, termed the distal regulatory region (DRR), that heretofore has been identified only in mice. Here, we identify DRR-related sequences in humans and show that DRR function is conserved in humans and mice. In addition, transcriptional activity of MyoD 5' flanking sequences in somites and limb buds is largely a composite of the individual specificities of the two enhancers. Deletion of fragment 3 resulted in dramatic but temporary expression defects in the hypaxial myotome and limb buds, suggesting that this regulatory region is essential for proper temporal and spatial patterning of MyoD expression. These data indicate that regulatory sequences in fragment 3 are important targets of embryonic signaling required for the initiation of MyoD expression. SN - 1058-8388 UR - https://www.unboundmedicine.com/medline/citation/11458388/Two_upstream_enhancers_collaborate_to_regulate_the_spatial_patterning_and_timing_of_MyoD_transcription_during_mouse_development_ L2 - https://doi.org/10.1002/dvdy.1138 DB - PRIME DP - Unbound Medicine ER -