Phosphorylation of histone H1 by P‐TEFb is a necessary step in skeletal muscle differentiation

Abstract

Positive transcription elongation factor b (P-TEFb), the complex of Cyclin T1 and CDK9, activates the transcription of many viral and eukaryotic genes at the point of mRNA elongation. The activity of P-TEFb has been implicated in the differentiation of a number of cell types, including skeletal muscle. In order to promote transcription, P-TEFb hyperphosphorylates RNA Pol II, thereby increasing its processivity. Our previous work identified histone H1 as a P-TEFb substrate during HIV-1 and immediate-early transcription. Here, we examine the role of P-TEFb phosphorylation of histone H1 during differentiation, using the myoblast cell line C2C12 as a model for skeletal muscle differentiation. We found that H1 phosphorylation is elevated in differentiating C2C12, and this phosphorylation is sensitive to P-TEFb inhibition. H1 phosphorylation was also necessary for the induction of three muscle marker genes that require P-TEFb for expression. Additionally, ChIP experiments demonstrate that H1 dissociates from muscle differentiation marker genes in C2C12 cells under active P-TEFb conditions. We determine that both P-TEFb activity and H1 phosphorylation are necessary for the full differentiation of C2C12 myoblasts into myotubes.

Effect of Exercise on Cardiac and Metabolic Outcomes in People Living With HIV

“…All but three of the studies in this review had a signifi cantly higher proportion of male to female participants, with as little as 13% females in one study (Smith et al, 2001). Recent trials have begun to close the gender gap by including more female participants Ogalha et al, 2011).…”

“…The other four studies in this review estimated VO 2 using treadmill speed and grade or resistance and revolutions per minute on a cycle ergometer (Dolan et al, 2006;Hand et al, 2008;Ogalha et al, 2011). Of those who measured VO 2 directly, two studies documented signifi cant improvements in VO 2max in the exercise groups compared to control or comparison groups (Lindegaard et al, 2008;Terry et al, 2006), one approached signifi cance ( p ϭ .09; Smith et al, 2001) and one showed no improvement (Baigis et al, 2002).…”

“…Exercise recommendations can be met through 30-60 min of moderate-intensity aerobic exercise 5 days/week or 20-60 min of vigorousintensity aerobic exercise 3 days/week (Garber et al, 2011). After extensive review of current exercise literature for adults living with HIV, the Cochrane Collaboration found that aerobic exercise conducted for at least 5 weeks, 3 times per week for at least 20 min may lead to signifi cant improvements in cardiopulmonary fi tness and body composition outcomes (O'Brien, Nixon, Tynan, & Glazier, 2010).…”

Proteomic and phosphoproteomic analyses of chromatin‐associated proteins from Arabidopsis thaliana

“…). Many PTMs and notably phosphorylation have been reported for H1 histone linkers in animals and some functional roles for H1 phosphorylation were also identified (e.g., ). Such knowledge is still missing in plants.…”

Use of ATP analogs to inhibit HIV-1 transcription

“…For that, we used cdk9 immunoprecipitated complexes from TNF-α treated OM10.1 cells (source of active kinase) and incubated them with histone H1 as a substrate. A number of substrates including histone H1 have been shown to be phosphorylated by cdk9 (O'Brien et al, 2010; O'Brien et al, 2012; Tian et al, 2012). Results in Panel E show that CR8#13 (10 and 50 nM; Lanes 4 and 5) effectively inhibited cdk9 activity to similar levels as Flavopiridol (10 nM; Lane6).…”