Speculative cartoon to `integrate isolated clues', and stimulate thought. A few interactions described for A-type lamins in the text are illustrated here, speculatively, in the context of lamin filaments near the nuclear inner membrane (IM) or associated with chromatin. Integral membrane proteins nesprin 1α (Nesprin) and emerin (EM) are embedded at the IM. Many other lamin-binding IM proteins are not depicted. NPC, nuclear pore complex. NS, nucleosome. OM, nuclear outer membrane. (Top left) Emerin, representing all LEM-domain proteins, binds BAF. BAF and MOK bind lamins in vitro and inhibit Crx-dependent gene activation in vivo, implicating both proteins in lamin-dependent gene-regulation events. Not depicted are potential gene-regulatory complexes involving nuclear membrane proteins LAP2b (Nili et al., 2001; Foisner, 2003) or lamin B receptor (Östlund and Worman, 2003). Emerin has many direct binding partners including nesprin-1α, lamins, actin (not depicted), BAF and several transcription regulators (not shown) (Bengtsson and Wilson, 2004). The number of distinct oligomeric complexes that include emerin is not known. (Top right) Lamin-binding enzyme 12(S)-lipoxygenase [12(S)-LOX] converts arachidonic acid (AA) to 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE]. We speculate that this reaction occurs in a signaling complex near the inner membrane, where 12(S)-HETE then activates lamin-bound protein kinase Cα (PKCα), leading to phosphorylation of unknown target proteins. (Bottom center) Pairwise interactions, summarized in the text, suggest that one or multiple oligomeric gene-regulation complexes might be formed by LAP2α, A-type lamins, retinoblastoma (Rb), E2F/DP heterodimers (gene-specific activators), chromatin-silencing histone deacetylase complex (HDAC), BAF and additional unidentified chromatin partners for LAP2α (Vlcek et al., 2002).