Abstract
The rapid, transient induction of 80-100 immediate-early (IE) genes upon mitogenic stimulation occurs irrespective of protein synthesis and is mediated by modification of existing proteins. Two mechanisms, not mutually exclusive, involving modification either of sequence-specific transcription factors or of structural chromatin proteins primed by pre-association with responsive effectors are conceivable. Here, we show that upon IE gene induction, the non-histone high-mobility-group protein HMG-14, but not the related protein HMG-17, becomes serine phosphorylated in its basic, amino-terminal region close to where it binds nucleosomal DNA. Phosphorylation, normally transient, occurs independent of transcription and is quantitative and prolonged during superinduction. Brief micrococcal nuclease digestion substantially releases HMG-14 from nuclei in the mononucleosome-bound state. Finally, mononucleosomes prepared from mitogen-stimulated, but not control, cells contain a mitogen-activated kinase that phosphorylates HMG-14 in vitro on the same site(s) as in intact cells. The association of HMG-14 and its mitogen-activated kinase with nuclease-sensitive mononucleosomes has implications for models of mitogen-stimulated IE gene induction.
| Original language | English |
|---|---|
| Pages (from-to) | 4524-4535 |
| Number of pages | 12 |
| Journal | EMBO Journal |
| Volume | 13 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - 25 Oct 1994 |
| Externally published | Yes |
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A mitogen- and anisomycin-stimulated kinase phosphorylates HMG-14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes. / Barratt, M. J.; Hazzalin, C. A.; Zhelev, N.; Mahadevan, L. C.
In: EMBO Journal, Vol. 13, No. 19, 25.10.1994, p. 4524-4535.Research output: Contribution to journal › Article
TY - JOUR
T1 - A mitogen- and anisomycin-stimulated kinase phosphorylates HMG-14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes
AU - Barratt, M. J.
AU - Hazzalin, C. A.
AU - Zhelev, N.
AU - Mahadevan, L. C.
PY - 1994/10/25
Y1 - 1994/10/25
N2 - The rapid, transient induction of 80-100 immediate-early (IE) genes upon mitogenic stimulation occurs irrespective of protein synthesis and is mediated by modification of existing proteins. Two mechanisms, not mutually exclusive, involving modification either of sequence-specific transcription factors or of structural chromatin proteins primed by pre-association with responsive effectors are conceivable. Here, we show that upon IE gene induction, the non-histone high-mobility-group protein HMG-14, but not the related protein HMG-17, becomes serine phosphorylated in its basic, amino-terminal region close to where it binds nucleosomal DNA. Phosphorylation, normally transient, occurs independent of transcription and is quantitative and prolonged during superinduction. Brief micrococcal nuclease digestion substantially releases HMG-14 from nuclei in the mononucleosome-bound state. Finally, mononucleosomes prepared from mitogen-stimulated, but not control, cells contain a mitogen-activated kinase that phosphorylates HMG-14 in vitro on the same site(s) as in intact cells. The association of HMG-14 and its mitogen-activated kinase with nuclease-sensitive mononucleosomes has implications for models of mitogen-stimulated IE gene induction.
AB - The rapid, transient induction of 80-100 immediate-early (IE) genes upon mitogenic stimulation occurs irrespective of protein synthesis and is mediated by modification of existing proteins. Two mechanisms, not mutually exclusive, involving modification either of sequence-specific transcription factors or of structural chromatin proteins primed by pre-association with responsive effectors are conceivable. Here, we show that upon IE gene induction, the non-histone high-mobility-group protein HMG-14, but not the related protein HMG-17, becomes serine phosphorylated in its basic, amino-terminal region close to where it binds nucleosomal DNA. Phosphorylation, normally transient, occurs independent of transcription and is quantitative and prolonged during superinduction. Brief micrococcal nuclease digestion substantially releases HMG-14 from nuclei in the mononucleosome-bound state. Finally, mononucleosomes prepared from mitogen-stimulated, but not control, cells contain a mitogen-activated kinase that phosphorylates HMG-14 in vitro on the same site(s) as in intact cells. The association of HMG-14 and its mitogen-activated kinase with nuclease-sensitive mononucleosomes has implications for models of mitogen-stimulated IE gene induction.
U2 - 10.1002/j.1460-2075.1994.tb06774.x
DO - 10.1002/j.1460-2075.1994.tb06774.x
M3 - Article
C2 - 7925294
AN - SCOPUS:0027941473
VL - 13
SP - 4524
EP - 4535
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 19
ER -