DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina

Joseph M. Zullo, Ignacio A. Demarco, Roger Piqué-Regi, Daniel J. Gaffney, Charles B. Epstein, Chauncey J. Spooner, Teresa R. Luperchio, Bradley E. Bernstein, Jonathan K. Pritchard, Karen L. Reddy, Harinder Singh

Research output: Contribution to journalArticlepeer-review

279 Scopus citations


A large fraction of the mammalian genome is organized into inactive chromosomal domains along the nuclear lamina. The mechanism by which these lamina associated domains (LADs) are established remains to be elucidated. Using genomic repositioning assays, we show that LADs, spanning the developmentally regulated IgH and Cyp3a loci contain discrete DNA regions that associate chromatin with the nuclear lamina and repress gene activity in fibroblasts. Lamina interaction is established during mitosis and likely involves the localized recruitment of Lamin B during late anaphase. Fine-scale mapping of LADs reveals numerous lamina-associating sequences (LASs), which are enriched for a GAGA motif. This repeated motif directs lamina association and is bound by the transcriptional repressor cKrox, in a complex with HDAC3 and Lap2β. Knockdown of cKrox or HDAC3 results in dissociation of LASs/LADs from the nuclear lamina. These results reveal a mechanism that couples nuclear compartmentalization of chromatin domains with the control of gene activity.

Original languageEnglish (US)
Pages (from-to)1474-1487
Number of pages14
Issue number7
StatePublished - Jun 22 2012

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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