Transcription elongation factor SPT6

Definition:

Transcription elongation factor which binds histone H3 and plays a key role in the regulation of transcription elongation and mRNA processing. Enhances the transcription elongation by RNA polymerase II (RNAPII) and is also required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. Besides chaperoning histones in transcription, acts to transport and splice mRNA by forming a complex with IWS1 and the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2), to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription. SUPT6H via its association with SETD1A, regulates both class-switch recombination and somatic hypermutation through formation of H3K4me3 epigenetic marks on activation-induced cytidine deaminase (AICDA) target loci. Promotes the activation of the myogenic gene program by entailing erasure of the repressive H3K27me3 epigenetic mark through stabilization of the chromatin interaction of the H3K27 demethylase KDM6A.

References:

[1]. Mirai Nakamura, et al. Spt6 levels are modulated by PAAF1 and proteasome to regulate the HIV-1 LTR. Retrovirology. 2012 Feb 8;9:13. [Content Brief]

[2]. Masaki Endoh, et al. Human Spt6 stimulates transcription elongation by RNA polymerase II in vitro. Mol Cell Biol. 2004 Apr;24(8):3324-36. [Content Brief]

[3]. A Hongjun Wang, et al. The histone chaperone Spt6 coordinates histone H3K27 demethylation and myogenesis. EMBO J. 2013 Apr 17;32(8):1075-86. [Content Brief]

[4]. F Wu-Baer, et al. Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 Tat-activation. J Mol Biol. 1998 Mar 27;277(2):179-97. [Content Brief]

[5]. Sunnie M Yoh, et al. The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing and export. Genes Dev. 2007 Jan 15;21(2):160-74. [Content Brief]

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