TY - JOUR
T1 - HP1α guides neuronal fate by timing E2F-targeted genes silencing during terminal differentiation
AU - Panteleeva, Irina
AU - Boutillier, Stéphanie
AU - See, Violaine
AU - Spiller, Dave G.
AU - Rouaux, Caroline
AU - Almouzni, Geneviève
AU - Bailly, Delphine
AU - Maison, Christèle
AU - Lai, Helen C.
AU - Loeffler, Jean Philippe
AU - Boutillier, Anne Laurence
PY - 2007/8/8
Y1 - 2007/8/8
N2 - A critical step of neuronal terminal differentiation is the permanent withdrawal from the cell cycle that requires the silencing of genes that drive mitosis. Here, we describe that the α isoform of the heterochromatin protein 1 (HP1) protein family exerts such silencing on several E2F-targeted genes. Among the different isoforms, HP1α levels progressively increase throughout differentiation and take over HP1γ binding on E2F sites in mature neurons. When overexpressed, only HP1α is able to ensure a timed repression of E2F genes. Specific inhibition of HP1α expression drives neuronal progenitors either towards death or cell cycle progression, yet preventing the expression of the neuronal marker microtubule-associated protein 2. Furthermore, we provide evidence that this mechanism occurs in cerebellar granule neurons in vivo, during the postnatal development of the cerebellum. Finally, our results suggest that E2F-targeted genes are packaged into higher-order chromatin structures in mature neurons relative to neuroblasts, likely reflecting a transition from a 'repressed' versus 'silenced' status of these genes. Together, these data present new epigenetic regulations orchestrated by HP1 isoforms, critical for permanent cell cycle exit during neuronal differentiation.
AB - A critical step of neuronal terminal differentiation is the permanent withdrawal from the cell cycle that requires the silencing of genes that drive mitosis. Here, we describe that the α isoform of the heterochromatin protein 1 (HP1) protein family exerts such silencing on several E2F-targeted genes. Among the different isoforms, HP1α levels progressively increase throughout differentiation and take over HP1γ binding on E2F sites in mature neurons. When overexpressed, only HP1α is able to ensure a timed repression of E2F genes. Specific inhibition of HP1α expression drives neuronal progenitors either towards death or cell cycle progression, yet preventing the expression of the neuronal marker microtubule-associated protein 2. Furthermore, we provide evidence that this mechanism occurs in cerebellar granule neurons in vivo, during the postnatal development of the cerebellum. Finally, our results suggest that E2F-targeted genes are packaged into higher-order chromatin structures in mature neurons relative to neuroblasts, likely reflecting a transition from a 'repressed' versus 'silenced' status of these genes. Together, these data present new epigenetic regulations orchestrated by HP1 isoforms, critical for permanent cell cycle exit during neuronal differentiation.
KW - E2F
KW - HP1́
KW - Heterochromatin
KW - Neuronal terminal differentiation
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=34547751335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547751335&partnerID=8YFLogxK
U2 - 10.1038/sj.emboj.7601789
DO - 10.1038/sj.emboj.7601789
M3 - Article
C2 - 17627279
AN - SCOPUS:34547751335
SN - 0261-4189
VL - 26
SP - 3616
EP - 3628
JO - EMBO Journal
JF - EMBO Journal
IS - 15
ER -