Histone Modification

Chromatin Modifier Modulates Gene Expression

Science Signaling  26 May 2009:
Vol. 2, Issue 72, pp. ec175
DOI: 10.1126/scisignal.272ec175

Modification of chromatin structure is usually thought of as a global, relatively nonspecific way of modulating gene expression. However, Wellen et al. (see the Perspective by Rathmell and Newgard) demonstrate that such regulation helps link growth factor–stimulated increases in metabolism to appropriate changes in gene expression. ATP-citrate lyase (ACL), which converts citrate to acetyl-CoA in the mitochondria of mammalian cells during metabolism of glucose, was also found to be present in the nucleus, where it might regulate activity of histone acetyl transferases (HATs) by controlling the availability of acetyl-CoA. Indeed, depletion of ACL from cultured human colon carcinoma cells specifically decreased histone acetylation in the nucleus but appeared not to affect the overall amount of acetylation of proteins in the cells. Loss of ACL in cultured mouse 3T3-L1 cells diminished the increase in histone acetylation normally associated with hormone-stimulated differentiation of these cells and inhibited the increase in expression of specific genes, such as that encoding the Glut4 glucose transporter. Thus ACL may help cells link metabolic activity to changes in gene expression.

K. E. Wellen, G. Hatzivassiliou, U. M. Sachdeva, T. V. Bui, J. R. Cross, C. B. Thompson, ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324, 1076–1080 (2009). [Abstract] [Full Text]

J. C. Rathmell, C. B. Newgard, A glucose-to-gene link. Science 324, 1021–1022 (2009). [Abstract] [Full Text]