CBP and p300 are histone acetyltransferases (HATs) that associate with and acetylate transcriptional regulators and chromatin. Mutations in their catalytic 'cores' are linked to genetic disorders, including cancer. Here we present the 2.8-Å crystal structure of the catalytic core of human p300 containing its bromodomain, CH2 region and HAT domain. The structure reveals that the CH2 region contains a discontinuous PHD domain interrupted by a RING domain. The bromodomain, PHD, RING and HAT domains adopt an assembled configuration with the RING domain positioned over the HAT substrate-binding pocket. Disease mutations that disrupt RING attachment led to upregulation of HAT activity, thus revealing an inhibitory role for this domain. The structure provides a starting point for understanding how chromatin-substrate targeting and HAT regulation are coupled and why mutations in the p300 core lead to dysregulation.

The Clavata3 (CLV3)/endosperm surrounding region (CLE) signaling peptides are encoded in large plant gene families. CLV3 and the other A-type CLE peptides promote cell differentiation in root and shoot apical meristems, whereas the B-type peptides (CLE41-CLE44) do not. Instead, CLE41 inhibits the differentiation of Zinnia elegans tracheary elements. To test whether CLE genes might code for antagonistic or synergistic functions, peptides from both types were combined through overexpression within or application onto Arabidopsis thaliana seedlings. The CLE41 peptide (CLE41p) promoted proliferation of vascular cells, although delaying differentiation into phloem and xylem cell lineages. Application of CLE41p or overexpression of CLE41 did not suppress the terminal differentiation of the root and shoot apices triggered by A-type CLE peptides. However, in combination, A-type peptides enhanced all of the phenotypes associated with CLE41 gain-of-function, leading to massive proliferation of vascular cells. This proliferation relied on auxin signaling because it was enhanced by exogenous application of a synthetic auxin, decreased by an auxin polar transport inhibitor, and abolished by a mutation in the Monopteros auxin response factor. These findings highlight that vascular patterning is a process controlled in time and space by different CLE peptides in conjunction with hormonal signaling.cambium ͉ hypocotyl ͉ RAM ͉ SAM ͉ TDIF I n higher plants, postembryonic organogenesis is mediated by meristems. These specialized structures provide a reservoir of undifferentiated stem cells as well as a limited population of proliferating cells, often referred to as transit-amplifying (TA) cells that are fated for differentiation (1). To date, molecular research has focused on the Arabidopsis primary meristems of root and shoot apices, but more recent studies have sought to dissect molecular programs underpinning the control of secondary meristems, including the vascular cambium (2, 3) that is a circumferential stem cell niche including the fusiform initials from which secondary xylem and phloem originate (2). During the course of differentiation, fusiform initial daughters take on a TA state to increase the population of xylem and phloem mother cells. Positioning and size of stem cell and TA cell populations, at least in root and shoot meristems, are controlled in a noncell-autonomous manner (1,4,5).This noncell-autonomous control of stem cell size and positioning has best been described in Arabidopsis primary meristems where a stable pool of undifferentiated stem cells are maintained by a feedback loop mechanism involving the Clavata (CLV) signaling pathway and the Wuschel (WUS) homeodomain transcription factor (6, 7). Similar regulatory mechanisms may be at work within root meristems, where the transcription factor WUS-related-homeobox 5 (WOX5) controls stem cell maintenance (8) and CLV3 and related genes can influence root patterning (9-11), although to date the regulation of WOX5 by a CLV-like pathway has not been demonstrated...