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Title: Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved

Abstract

Human myocyte-specific enhancer binding factor 2C (hMEF2C) belongs to the MEF2 subfamily of the MADS (MCM1, AGAMOUS, DEF A, serum response factor) family of transcription factors. Members of the MADS family share a conserved domain - the MADS domain - that is necessary for DNA binding. Highly conserved versions of the MADS domain and of an adjacent domain that is known as the MEF2 domain are found in members of the MEF2 subfamily. Both of these domains are necessary for binding to the MEF2 regulatory element. This regulatory element is known to be functionally important in a variety of muscle-specific genes and possibly in the brain creatine kinase gene. The MEF2C gene product activates transcription by binding to the MEF2 element. hMEF2C is expressed at high levels in postmitotic neurons in the brain, where it is most abundant in the cerebral cortex, and is also expressed in differentiated myotubes. Several lines of evidence suggest the existence of a rat homologue of MEF2C, and a mouse homologue has been cloned. The mouse gene was mapped to mouse chromosome 13 in a region that is syntenic to human 5q13-q15. 12 refs., 1 fig.

Authors:
;  [1]; ;  [2]
  1. Harvard Medical School, Boston, MA (United States)
  2. Yale Univ. School of Medicine, New Haven, CT (United States) [and others
Publication Date:
OSTI Identifier:
443890
Resource Type:
Journal Article
Resource Relation:
Journal Name: Genomics; Journal Volume: 29; Journal Issue: 3; Other Information: PBD: 10 Oct 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; TRANSCRIPTION FACTORS; GENETIC MAPPING; BIOLOGICAL EVOLUTION; GENE REGULATION; GENE MUTATIONS; HUMAN CHROMOSOME 5; CHROMOSOMES; CREATINE; PHOSPHOTRANSFERASES; MICE; DNA HYBRIDIZATION; FLUORESCENCE; BUDR; BANDING TECHNIQUES; HEREDITARY DISEASES; POLYMERASE CHAIN REACTION

Citation Formats

Krainc, D., Lipton, S.A., Haas, M., and Ward, D.C.. Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved. United States: N. p., 1995. Web. doi:10.1006/geno.1995.9927.
Krainc, D., Lipton, S.A., Haas, M., & Ward, D.C.. Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved. United States. doi:10.1006/geno.1995.9927.
Krainc, D., Lipton, S.A., Haas, M., and Ward, D.C.. 1995. "Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved". United States. doi:10.1006/geno.1995.9927.
@article{osti_443890,
title = {Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved},
author = {Krainc, D. and Lipton, S.A. and Haas, M. and Ward, D.C.},
abstractNote = {Human myocyte-specific enhancer binding factor 2C (hMEF2C) belongs to the MEF2 subfamily of the MADS (MCM1, AGAMOUS, DEF A, serum response factor) family of transcription factors. Members of the MADS family share a conserved domain - the MADS domain - that is necessary for DNA binding. Highly conserved versions of the MADS domain and of an adjacent domain that is known as the MEF2 domain are found in members of the MEF2 subfamily. Both of these domains are necessary for binding to the MEF2 regulatory element. This regulatory element is known to be functionally important in a variety of muscle-specific genes and possibly in the brain creatine kinase gene. The MEF2C gene product activates transcription by binding to the MEF2 element. hMEF2C is expressed at high levels in postmitotic neurons in the brain, where it is most abundant in the cerebral cortex, and is also expressed in differentiated myotubes. Several lines of evidence suggest the existence of a rat homologue of MEF2C, and a mouse homologue has been cloned. The mouse gene was mapped to mouse chromosome 13 in a region that is syntenic to human 5q13-q15. 12 refs., 1 fig.},
doi = {10.1006/geno.1995.9927},
journal = {Genomics},
number = 3,
volume = 29,
place = {United States},
year = 1995,
month =
}
  • MEF2 genes belong to the MADS box family of transcription factors and encode proteins that bind as homo- and heterodimers to a consensus CTA(T/A){sub 4}TAG/A sequence present in the regulatory regions of numerous muscle-specific and growth inducible genes. Sequence analysis of human MEF2 cDNA clones suggested that they arose from alternatively spliced transcripts of four different genes, termed MEF2A-D. We have mapped the MEF2 genes to human chromosomal regions by identifying unique sequences in the 5{prime} or 3{prime} untranslated regions of each clone and using these sequences as PCR primers on the DNA of a human-rodent hybrid clone panel informativemore » for different regions of the human genome. The localization of MEF2A to chromosome 15q, MEF2B to 19q, MEF2C to 5q, and MEF2D to 1q verifies the existence of at least four distinct loci for members of this gene family. The same PCR primers were used to identify individual YAC clones for each gene. Such isolated clones are now being used for fluorescence in situ hybridization for high resolution chromosomal regional assignment.« less
  • Hypoxia-inducible factor 1 (HIF-1) is a basic helix-loop-helix transcription factor that mediates homeostatic responses to hypoxia. HIF-1 is a heterodimer consisting of HIF-1{alpha} which is encoded by the HIF1A gene, complexes with HIF-1{beta}, which is encoded by the ARNT gene. In this paper we report the assignment of Hif1a and HIF1A to mouse chromosome 12 and human chromosome 14, respectively. HIF1A was assigned to human chromosome 14q21-q24 by analysis of somatic cell hybrids and by fluorescence in situ hybridization. Hif1a was localized by interspecific backcross analysis within a region of mouse chromosome 12 encompassing >30 cM that demonstrates conservation ofmore » synteny with a region of human chromosome 14 extending from PAX9 at 14q12-q13 to IGHC at 14q32.33. 12 refs., 2 figs.« less
  • The MEF2 genes belong to the MADS box family of transcription factors and encode proteins that bind as homo- and heterodimers to a consensus CTA(T/A){sub 4}TAG/A sequence, which is present in the regulatory regions of numerous muscle-specific and growth-inducible genes. Sequence analysis of human MEF2 cDNA clones suggests that they arose from alternatively spliced transcripts of four different genes, termed MEF2A-D. We have mapped the MEF2 genes to human chromosomal regions by identifying unique sequences in the MEF2 cDNA clones and using these sequences as PCR primers on the DNA of human-rodent hybrid clone panels that are informative for differentmore » regions of the human genome. PCR primers were also used to identify individual YAC clones for two of the genes, MEF2A and MEF2C, and a PCR product was used to identify cosmid clones for MEF2B. Genetic and physical mapping information available from genome databases on markers contained within YAC and cosmid clones provided independent assignments for those genes. Inter-Alu PCR painting probes of YAC clones were used as probes for high-resolution chromosomal regional assignment by fluorescence in situ hybridization. The localization of MEF2A to chromosome 15q26, MEF2B to 19p12, MEF2C to 5q14, and MEF2D to 1q12-q23 verifies the existence of at least four distinct loci for members of this gene family. 37 refs., 4 figs., 1 tab.« less
  • A segment of 1,022 base pairs (bp) of the 5{prime}-flanking region of the human albumin gene, fused to a reporter gene, directs hepatoma-specific transcription. Three functionally distinct regions have been defined by deletion analysis: a negative element located between bp {minus}673 and {minus}486, an enhancer essential for efficient albumin transcription located between bp {minus}486 and {minus}221, and a promoter spanning a region highly conserved throughout evolution. Protein-binding studies have demonstrated that a liver {ital trans}-acting factor which interacts with the enhancer region is the well-characterized transcription factor LF-B1, which binds to promoters of several liver-specific genes. A synthetic oligodeoxynucleotide containingmore » the LF-B1-binding site is sufficient to act as a tissue-specific transcriptional enhancer when placed in front of the albumin promoter. The fact that the same binding site functions in both an enhancer and a promoter suggests that these two elements influence the initiation of transcription through similar mechanisms.« less
  • Comparison of human sequences with the DNA of other mammals is an excellent means of identifying functional elements in the human genome. Here we describe the utility of high-density oligonucleotide arrays as a rapid approach for comparing human sequences with the DNA of multiple species whose sequences are not presently available. High-density arrays representing approximately 22.5 Mb of nonrepetitive human chromosome 21 sequence were synthesized and then hybridized with mouse and dog DNA to identify sequences conserved between humans and mice (human-mouse elements) and between humans and dogs (human-dog elements). Our data show that sequence comparison of multiple species providesmore » a powerful empiric method for identifying actively conserved elements in the human genome. A large fraction of these evolutionarily conserved elements are present in regions on chromosome 21 that do not encode known genes.« less