Abstract
BackgroundThe elongation phase, like other steps of transcription by RNA Polymerase II, is subject to regulation. The positive transcription elongation factor b (P-TEFb) complex allows for the transition of mRNA synthesis to the productive elongation phase. P-TEFb contains Cdk9 (Cyclin-dependent kinase 9) as its catalytic subunit and is regulated by its Cyclin partners, Cyclin T1 and Cyclin T2. The HIV-1 Tat transactivator protein enhances viral gene expression by exclusively recruiting the Cdk9-Cyclin T1 P-TEFb complex to a RNA element in nascent viral transcripts called TAR. The expression patterns of Cyclin T1 and Cyclin T2 in primary monocytes and CD4+ T cells suggests that Cyclin T2 may be generally involved in expression of constitutively expressed genes in quiescent cells, while Cyclin T1 may be involved in expression of genes up-regulated during macrophage differentiation, T cell activation, and conditions of increased metabolic activity To investigate this issue, we wished to identify the sets of genes whose levels are regulated by either Cyclin T2 or Cyclin T1.FindingsWe used shRNA lentiviral vectors to stably deplete either Cyclin T2 or Cyclin T1 in HeLa cells. Total RNA extracted from these cells was subjected to cDNA microarray analysis. We found that 292 genes were down- regulated by depletion of Cyclin T2 and 631 genes were down-regulated by depletion of Cyclin T1 compared to cells transduced with a control lentivirus. Expression of 100 genes was commonly reduced in either knockdown. Additionally, 111 and 287 genes were up-regulated when either Cyclin T2 or Cyclin T1 was depleted, respectively, with 45 genes in common.ConclusionsThese results suggest that there is limited redundancy in genes regulated by Cyclin T1 or Cyclin T2.
Highlights
The elongation phase, like other steps of transcription by RNA Polymerase II, is subject to regulation
Core positive transcription elongation factor b (P-TEFb) consists of Cyclin dependent kinase 9 (Cdk9) as the catalytic subunit, a Cyclin subunit either Cyclin T1 T2 or K, and a protein known as Brd4 that is involved in directing core P-TEFb to active genes that are marked by
This expression pattern of Cyclin T2 and Cyclin T1 in quiescent vs. activated monocytes and CD4+ T cells suggests that Cyclin T2 may be generally involved in expression of constitutively expressed genes in quiescent cells, while Cyclin T1 may be involved in expression of genes up-regulated during macrophage differentiation, T cell activation, and conditions of increased metabolic activity [14]
Summary
The elongation phase, like other steps of transcription by RNA Polymerase II, is subject to regulation. Cyclin T1 is expressed at low levels in monocytes and it is strongly up-regulated by a post-transcriptional mechanism when the cells are induced to differentiate to macrophages [8,9]. Cyclin T1 levels are low in resting CD4+ T cells and are strongly up-regulated following T cell activation by a post-transcriptional mechanism [11,12,13] This expression pattern of Cyclin T2 and Cyclin T1 in quiescent vs activated monocytes and CD4+ T cells suggests that Cyclin T2 may be generally involved in expression of constitutively expressed genes in quiescent cells, while Cyclin T1 may be involved in expression of genes up-regulated during macrophage differentiation, T cell activation, and conditions of increased metabolic activity [14]
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