Given a set $\mathcal{F}$ of graphs, we call a copy of a graph in $\mathcal{F}$ an $\mathcal{F}$-graph. The $\mathcal{F}$-isolation number of a graph $G$, denoted by $ι(G,\mathcal{F})$, is the size of a smallest set $D$ of vertices of $G$ such that the closed neighbourhood of $D$ intersects the vertex sets of the $\mathcal{F}$-graphs contained by $G$ (equivalently, $G - N[D]$ contains no $\mathcal{F}$-graph). Thus, $ι(G,\{K_1\})$ is the domination number of $G$. For any integer $k \geq 1$, let $\mathcal{F}_{1,k}$ be the set of regular graphs of degree at least $k-1$, let $\mathcal{F}_{2,k}$ be the set of graphs whose chromatic number is at least $k$, and let $\mathcal{F}_{3,k}$ be the union of $\mathcal{F}_{1,k}$ and $\mathcal{F}_{2,k}$. Thus, $k$-cliques are members of both $\mathcal{F}_{1,k}$ and $\mathcal{F}_{2,k}$. We prove that for each $i \in \{1, 2, 3\}$, $\frac{m+1}{{k \choose 2} + 2}$ is a best possible upper bound on $ι(G, \mathcal{F}_{i,k})$ for connected $m$-edge graphs $G$ that are not $k$-cliques. The bound is attained by infinitely many (non-isomorphic) graphs. The proof of the bound depends on determining the graphs attaining the bound. This appears to be a new feature in the literature on isolation. Among the result's consequences are a sharp bound of Fenech, Kaemawichanurat and the present author on the $k$-clique isolation number and a sharp bound on the cycle isolation number.