TY - JOUR
T1 - Phenotypic transcription factors epigenetically mediate cell growth control
AU - Ali, Syed A.
AU - Zaidi, Sayyed K.
AU - Dacwag, Caroline S.
AU - Salma, Nunciada
AU - Young, Daniel W.
AU - Shakoori, Abdul R.
AU - Montecino, Martin A.
AU - Lian, Jane B.
AU - Van Wijnen, Andre J.
AU - Imbalzano, Anthony N.
AU - Stein, Gary S.
AU - Stein, Janet L.
PY - 2008/5/6
Y1 - 2008/5/6
N2 - Ribosomal RNA (rRNA) genes are down-regulated during osteogenesis, myogenesis, and adipogenesis, necessitating a mechanistic understanding of interrelationships between growth control and phenotype commitment. Here, we show that cell fate-determining factors [MyoD, myogenin (Mgn) , Runx2, C/EBPβ] occupy rDNA loci and suppress rRNA expression during lineage progression, concomitant with decreased rRNA expression and reciprocal loss of occupancy by c-Myc, a proliferation-specific activator of rRNA transcription. We find interaction of phenotypic factors with the polymerase I activator upstream binding factor UBF-1 at interphase nucleoli, and this interaction is epigenetically retained on mitotic chromosomes at nucleolar organizing regions. Ectopic expression and RNA interference establish that MyoD, Mgn, Runx2, and C/EBPβ each functionally suppress rRNA genes and global protein synthesis. We conclude that epigenetic control of ribosomal biogenesis by lineage-specific differentiation factors is a general developmental mechanism for coordinate control of cell growth and phenotype.
AB - Ribosomal RNA (rRNA) genes are down-regulated during osteogenesis, myogenesis, and adipogenesis, necessitating a mechanistic understanding of interrelationships between growth control and phenotype commitment. Here, we show that cell fate-determining factors [MyoD, myogenin (Mgn) , Runx2, C/EBPβ] occupy rDNA loci and suppress rRNA expression during lineage progression, concomitant with decreased rRNA expression and reciprocal loss of occupancy by c-Myc, a proliferation-specific activator of rRNA transcription. We find interaction of phenotypic factors with the polymerase I activator upstream binding factor UBF-1 at interphase nucleoli, and this interaction is epigenetically retained on mitotic chromosomes at nucleolar organizing regions. Ectopic expression and RNA interference establish that MyoD, Mgn, Runx2, and C/EBPβ each functionally suppress rRNA genes and global protein synthesis. We conclude that epigenetic control of ribosomal biogenesis by lineage-specific differentiation factors is a general developmental mechanism for coordinate control of cell growth and phenotype.
KW - C/EBP
KW - Mitosis
KW - MyoD
KW - Runx
UR - http://www.scopus.com/inward/record.url?scp=44349121057&partnerID=8YFLogxK
U2 - 10.1073/pnas.0800970105
DO - 10.1073/pnas.0800970105
M3 - Article
C2 - 18445650
AN - SCOPUS:44349121057
SN - 0027-8424
VL - 105
SP - 6632
EP - 6637
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 18
ER -