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Epigenetic Modifications at the Human Growth Hormone Locus Predict Distinct Roles for Histone Acetylation and Methylation in Placental Gene Activation

Departments of Genetics and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104

Address all correspondence and requests for reprints to: Nancy E. Cooke, 752b Clinical Research Building, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104. E-mail: necooke{at}mail.med.upenn.edu.

Developmental control of eukaryotic gene expression is tightly linked to alterations in chromatin structure. Studies of the hGH multigene cluster suggest that the four placental genes are activated by a pathway of histone modification distinct from the pathway leading to activation of the single pituitary hGH-N gene. The relationship between histone acetylation and hGH-N activation in the pituitary has been previously defined using a combination of epigenetic mapping and transgenic analyses. The repeated gene structures within the hGH cluster had been an impediment to comparable analysis of placental gene activation. In the present report we defined patterns of core histone acetylation and methylation within and flanking the hGH cluster in human placental chromatin. These data highlight differences between placental and pituitary pathways of transcriptional control at the hGH cluster and suggest that selective activation of the placental genes reflects distinct roles for histone acetyltransferase and histone methyltransferase coactivator complexes.

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