HMG Domain Superfamily of DNA ‐bending Proteins: HMG , UBF , TCF , LEF , SOX , SRY and Related Proteins

Abstract

SRY , the Y‐chromosome‐encoded male sex‐determining factor, is the signature member of a larger family of related transcription factors, the SOX proteins. SOX proteins are related by a DNA ( deoxyribonucleic acid )‐binding domain known as the HMG ( high mobility group ) domain, which in turn unites a larger superfamily of proteins. SRY and SOX proteins are thought to regulate gene transcription through binding to specific DNA sequence motifs and causing the DNA to bend – a property of so‐called architectural transcription factors. Similarly, a related family of proteins, including TCF‐1 ( T‐cell factor 1 ), LEF‐1 ( lymphoid enhancer factor 1 ) and their relatives, regulates transcription by virtue of sequence‐specific DNA binding. A third family, the true or canonical HMG proteins, differs by containing multiple HMG domains, not binding to specific target DNA sequences, and having poorly defined roles. Here, we examine the diversity, origins, molecular functions and biological roles of the HMG domain superfamily. Key Concepts: The 80 amino acid HMG domain characterizes a superfamily of proteins found in plants and animals. HMG domain proteins associate with DNA and usually bend it, thereby influencing transcription of genes. The most ancient family of these proteins, represented by the canonical HMG proteins HMG‐1 and HMG‐2, have multiple HMG domains, and do not bind to any specific DNA sequences. Genes encoding canonical HMG proteins may have evolved into two further families of genes encoding proteins that have single HMG domains and bind to specific DNA sequence motifs. These families include SRY (the mammalian Y‐linked sex‐determining factor) and the SOX, TCF‐1 and LEF‐1 transcription factors. Unlike canonical HMG proteins, these other HMG domain proteins have specific, important and well‐defined biological roles, particularly in embryonic development.

SOX10, a novel HMG-box-containing tumor suppressor, inhibits growth and metastasis of digestive cancers by suppressing the Wnt/β-catenin pathway

“…For example, during Schwann cell development, SOX10 cooperates with OCT6/BRN2 to upregulate the Krox20 gene. However, during melanocyte development, SOX10 is partnered with PAX3 and activates the gene encoding MITF [ 5 , 42 ]. In melanoma, SOX10 haploinsufficiency abrogates Nras Q61K -driven tumor initiation as well as progression [ 22 ].…”

It’s All in the Genes: The Regulatory Pathways of Sexual Reproduction in Filamentous Ascomycetes

“…In addition to PaHMG8, two other HMG box proteins, PaHMG5 and PaHMG6, are also responsible for the tight regulation of the two MAT genes and their transcription networks [22]. Transcription factors that possess the HMG box domain are involved in a multitude of biological processes, with a particular importance in pathways associated with sexual reproduction in fungi [23].…”

Identification of genetic bases of male fertility inPyricularia oryzaeby Genome Wide Association Study (GWAS)

“…Proteins encoded by HMG-box genes are transcription factors able to bind DNA, facilitate nucleoprotein assembly (Giese et al, 1992), and their role in gamete production vary between species (Koopman, 2010). The mating-type system is not required for the production of gametes in Podospora anserina (Coppin et al, 1993) or in Neurospora crassa (Ferreira et al, 1998).…”

“…In P. oryzae , the two idiomorphs of the MAT1 locus ( MAT1.1 and MAT1.2 ) correspond to 2 and 3 genes respectively, one of them encoding a protein containing an alpha-box DNA binding domain (Kanamori et al, 2007). Proteins encoded by HMG-box genes are transcription factors able to bind DNA, facilitate nucleoprotein assembly (Giese et al, 1992), and their role in gamete production vary between species (Koopman, 2010). The mating-type system is not required for the production of gametes in Podospora anserina (Coppin et al, 1993) or in Neurospora crassa (Ferreira et al, 1998).…”